Prologue
This guide assumes you have a basic understanding of core game mechanics. This does not contain story spoilers, but may make some gameplay sections less exciting. You can view the text-only version of this page on the sidebar, and save it to check off during your playthrough.
If you have not played, I personally advise playing the game on Normal difficulty, and ignoring this guide for the time being. You will have to replay the game a few times, due to challenges and extra modes, so theres no point in min-maxxing the first run. The reason I recommend Normal is so you become more acquainted with how the game works, so when you run thru on Hard, you're not completely lost/way too squishy.
When you complete the main campaign for the first time, you will unlock two new modes. "Leech Hunter" and "Wesker Mode". LH has you in the main mansion, collecting green and blue leech charms. Keep in mind that the difficulty of LH is determined by the mode you finished the game on. And WM is a replay of the campaign, but replacing Billy with RE5 Wesker. WM is always on Normal difficulty, and hidden in the "Extras" menu.
About Saves
When you select a difficulty, that save will be locked to that difficulty. Any achievement progress, or bonus weapons, will not carry over to a new game. So if you say, combine a red/green herb on a Normal save, and then get the rest of the herb combinations on a Hard save without getting red/green, you will not get the achievement for combining all herbs.
When you have completed a campaign, the game will ask you to save. This is your "finished" file, and you should overwrite the old save you've been using. Selecting this file will show you a few options, you should always select "Once Again". This saves your achievement progress (such as herb combinations, weapons used, files read,) and bonus weapons obtained from LH, so NEVER OVERWRITE IT or select "RESTART"!
From this "finished file" menu, you will also see "Extra Game", which brings you to Leech Hunter. We will get to Leech Hunter's save notes when we get to that section, so don't touch it yet.
Linux Setup
If you're a dirty Windows user, you can skip this. If you're playing on Steam Deck, or Linux in general, you may notice some funny graphics issues. Don't you just love games made on old engines? And these graphics issues aren't minor little oddities either, like some lines appearing in the rain, but instead..
..Yowza.
If you have run the game before applying the fixes, you will need to delete the old Proton prefix. Navigate from root to ".steam > steam > steamapps > compatdata > 339340" and delete the final folder with the numbers. (This is RE0's game ID, it will always be the same!)
There are two possible fixes, one for Steam Deck and another for general computers. I attempted the normal computer fix on Steam Deck, which did not work. Your mileage may vary! So if one fix doesn't work, delete the Proton folder again and try the other method.
The fix for my general desktop (Linux Mint XFCE 21.3) was to download Proton-GE (find instructions for your distro) and attempt one of the following versions: GE-Proton7-49, GE-Proton7-37, and GE-Proton7-50. Restart Steam, go to properties and select one of these versions. If one version doesn't work, you can uninstall it thru GE-Proton.
For Steam Deck, set your Proton version to 9.0-4, and download ProtonTricks. If RE0 doesn't appear in the ProtonTricks list, run the game with 9.0-4 applied and return. From the ProtonTricks menu, navigate "Select the default wineprefix > Install a Windows DLL or component" and install BOTH "wmp11" and "wmv9vcm". Wait a few minutes, some prompts may appear, or you may see them appear for a brief second when you swap back to Gaming Mode. (Which is fine) And run the game.
If somehow neither of these fixes work, look for other solutions on ProtonDB.
Story [Unmissable]
These are unmissable for playing thru the main campaign.
"Taking The Sting Out": Defeat Stinger.
"Train Complete": Complete the train.
"Centurion Disciplinarian": Defeat Centurion.
"Training Facility Complete": Complete the training facility.
"Die, Devil Bird!": Defeat Infected Bat.
"Proto Tyrant Down": Fight off the Proto Tyrant.
"Laboratory Complete": Complete the laboratory.
"Proto Tyrant Down Again": Defeat the Proto Tyrant.
"Hey, Queenie! Feast On This!": Defeat Queen Leech.
"Treatment Plant Complete": Complete the treatment plant.
Story [Missable]
These are for things you do in the main campaign.
"Fashion Plate": Change into a costume.
...Yes I know it's not really story oriented, but I'm not making a whole other section just for this. In the inventory menu, select your character's personal item (mixing kit for Rebecca, lighter for Billy) and select "swap", it should change to a suitcase. Select "use", and swap to an outfit of your choosing. Snazzy :D!
"I'm A Medic, Not A Bodybuilder": Try to push something heavy with Rebecca.
At one point, you will use Billy's lighter to unlock a door in the Library. Once the room is safe, take Rebecca up the ledge to the bookcase where you get the white book, and attempt to push it.
"Green Is The Color": Use a Green Chemical.
The green chemical is found in the Infirmary, 2F of the Training Facility mansion, same hallway as the chess puzzle. Rebecca's special ability is her mixing kit, so swap to her and grab it. Then, while in front of the canister, use the green chemical from the menu, and then re-add it (canisters have infinite uses) back to your mixing kit. Now, some things about the green chemical you should note.. DON'T USE IT! If you are poisoned, (which I believe is only possible by the giant spiders) you can use the green chemical to heal yourself. But it is much, much, so much better to use the abundance of blue herbs for this. At one point in your playthrough, you'll be between sending Billy or Rebecca upstairs into the Laboratory using the grappling hook, and once they're up there, they won't be able to come down. Many guides will have you sending Billy upstairs, which is optimal for his beefy HP and also because Rebecca being downstairs is alot faster for her to combine with the red chemical canister to progress. What they don't tell you, is if you used your green chemical, it is an absolute pain in the ass and NIGHTMARE to backtrack back into the Infirmary in the mansion to get it again. Eliminator apes will guard the way, and it's just not the worth of bullets to get past them. Yes, I am speaking out of personal headache for not knowing this, and having to reload an older save because of the apes. Make sure you have the green chemical with you before leaving the mansion!
"Apprentice Of Unlocking": Obtain all keys and use them all.
There is only one missable key thru the entire campaign. And that is the key to create the custom handgun, (which will also unlock you "Custom To Bust 'Em") which is found on the B3 floor of the Facility Basement, guarded by two Plague Crawlers (those ugly scorpion looking things). Continue to the controller room ahead, and walk beyond the switch to find a locker. Use the key here.
"Calm The Zombie Nerves": Play the piano using Rebecca.
To get one of the tablets, you will need to power a lift outside the mansion using a battery. The battery is located in a bar on the 2F of the Training Facility mansion. Normally, you should use Billy to unlock the door by playing the piano. Use Rebecca first to get the achievement.
"On Leather Wings": Get picked up by the Infected Bat.
I'm placing this here, since it can take a while to get to the Infected Bat boss fight, and also because there is another achievement related to this fight listed below. Simply stand around and get picked up.
"Winged Spawn Of Satan": Defeat 16 bats in the church.
This is related to the aforementioned Infected Bat boss fight. As soon as you exit the safe room in the Church, the Infected Bat will spawn. You likely have noticed the tiny bats that spawn with it, you need to kill 16 of these. Simple, right? No :D This is pretty tedious, and it is absolutely mandatory you create a save in the safe room before doing this. Do not take crazy high-powered weapons with you, you need the Infected Bat alive for the bats to spawn. Make sure you have some herbs, and a "smaller bullet" weapon to pick off the bats with. Keep in mind, you can enter the safe room again and also go back outside to your partner if needed. I recommend using Billy, for his larger HP. My strategy was as follows: At 50% HP, 8 bats spawn. Stand in the corner outside the safe room door, point your gun upwards and "tap" fire the tiny bats. When the big bat gets close, run back inside the safe room to reset the positions. Once you have killed the first 8 bats, save again, this is your checkpoint. Once the main bat is at 25% health, tiny bats spawn continuously. Repeat until achievement unlocks.
Enemies
Related to the people trying to sell you car insurance thru the game.
"Sit, Boy, Sit! Good Dog": Break free of a Cerberus while they are biting you or trying to push you down.
Cerberus is the dogs, found mainly in the Train section.
"Guns Are Too Quick": Defeat an enemy with a knife.
When zombies are knocked down, without a crtiical headshot, they are likely to get back up. Run over to a downed zombie and slice at them for a bit until they fully die. You will know a zombie is fully dead when a pool of blood appears under them, and they make a funny death rattle.
"Zero In": Defeat an enemy with a critical-hit headshot.
To get this easy, take a shotgun, let a zombie approach, and aim the shotgun upwards. It may seem like the zombie needs to be really close, but the hitbox is super forgiving.
"Misdirected Hostility": Destroy a zombie's legs.
Same method as above, just aim the shotgun downwards to their legs.
"Dead, Dead, Deadski": Defeat a zombie by stomping on them.
Some zombies are sticking out from under tables or beds. When approaching them, the kick animation plays. I believe this can happen with both characters, but try with Billy first if you're going into a room you know has them.
"Here I Come To Save The Day": Attack an enemy to save your partner who is grappling with that enemy.
Set your partner to idle or without a weapon, and shoot whatever is locking them in the "grab" animation. Most easiest with zombies.
"Burned Alive": Defeat an enemy by burning them.
Can be done with molotov or napalm grenade. Will likely be obtained alongside the achievement below.
"How 'Bout A Light, Bud?": Defeat Mimicry Marcus with a molotov cocktail or a napalm grenade.
Mimicry Marcus is this weird wire-y looking guy who has the whistling sounding music. You'll know because he kicks your ass- The easiest and quickest way to kill him is with FYRA! So save your molotovs for encounters with him.
"Alley-oop!": Shoot down a Hunter or an Eliminator while they are jump attacking in the air.
Hunters are those reptile looking things, Eliminators are the apes.
File Checklist
"Fileophile": Read all files.
This can be done in a single playthrough, if diligent. If you did not get all files in a single playthrough, remember the "Once Again" selection I told you about earlier. There are 29 files total. I'm unsure if this matters, but to be absolutely certain all files count, make sure you reach the end of their page.
RELATED TO PROGRESSION:
[ ] Player's Manual 1
[ ] Player's Manual 2
[ ] Hookshot Operator's Manual
[ ] Brake Operation Manual
[ ] Microfilm Image
[ ] Marcus' Diary 1
[ ] Court Order for Transportation
[ ] Old Photograph
[ ] Gate Operation Manual
TRAIN:
[ ] Investigation Orders - Room 201.
[ ] Passenger's Diary - Room 202.
[ ] Note from Conductor - Conductor room.
[ ] Notice to Supervisors - In front of the stairs you go up where Rebecca is saved by Billy for the first time.
TRAINING FACILITY:
[ ] Notice to All Staff - Inside the room where you grab the crank. Grab before the crank, to avoid the crows.
[ ] Regulations For The Trainees - Conference room, the one where you insert the disk later.
[ ] Assistant Directors's Diary - Past the fire door, in the hallway that also leads to the Library.
[ ] A Verse of Poetry - Inside the fireplace room, where you grab Microfilm B.
[ ] First Investigation Unit Notes - Infirmary.
[ ] Correctional Institude Inmates List - Inside the basement save room.
[ ] About Power Regulator - Inside the torture room, the one where Rebecca gets lifted by Billy into.
[ ] Management Trainee's Diary - After lighting the animal statue puzzle, a gate will open. It's the door at the end of the small hall.
LABORATORY:
[ ] Marcus's Diary 2 - First save room upon exiting elevator.
[ ] Laboratory Manager's Diary - Leech capsule room with Mimicry Marcus, in the chair upon climbing up the hole.
[ ] Leech Growth Records - In room with gas chamber.
[ ] Investigator's Report - In room with service lift.
[ ] B.O.W Report - Inside room with two Hunters.
TREATMENT PLANT:
[ ] Investigator's Report 2 - In generator room, climbing ladder where red chemical canister is, near dead body.
[ ] About Battery Fluid - Lodgings, the room with bunkbeds and a typewriter.
[ ] Treatment Plant Manager's Diary - Cargo room, with the elevator you go down to fight Proto Tyrant.
Herb Combinations
"Find Time To Combine": Combine every type of herb with each other.
It is possible to do in a single playthrough, but it's a bit tedious, and you will likely need to use herbs you're saving for combinations. Write down the herbs you've done in your first playthrough, and get the rest with "Once Again".
[ ] Green + Green
[ ] Green + Green + Green
[ ] Green + Red
[ ] Green + Blue
[ ] Green + Green + Blue
[ ] Green + Blue + Red
Leech Hunter
Okay, time for the most boring yet rewarding part. Fun with leeches! To refresh your memory, after completing the main campaign, you will get Leech Hunter under "Extra Game". You will be placed back in the mansion, and have to collect green and blue leech charms. The reason Leech Hunter is so wonderful, are the badass weapons it gives you, including infinite ammo! And there is no time limit requirement for them, just how many charms you get.
When you complete Leech Hunter, it will prompt you to save your game. ONLY save if you have gotten rank A. Using weapons from Leech Hunter will not void your challenge runs (which we will be talking about soon) and makes them so much easier.
"Trying Out New Things": Play Leech Hunter.
"A Weird Interest In Leeches": Finish Leech Hunter with rank A.
"Leech-Shaped Hole In My Heart": Finish Leech Hunter with rank E or above.
"Distracted From The Hunt": Defeat all enemies in Leech Hunter.
And now, I am going to lead you to someone much more knowledgable in leeches then I could ever be. Optinoob has wonderful guide videos on LH, and explains what you need to do in incredible detail. Consult his guide here, for the above.
"Who Needs Partners?": Collect all of only one color of Leech Charms.
Again, please consult Optinoob's video.
"I Have The Touch": Defeat Mimicry Marcus for the first time only using a knife.
This might seem odd to place here, but I swear this will save you so much time. As soon as you load in, switch to Billy and take the first aid spray from Rebecca. Go to the kitchen and grab the knife off of the counter, and go to the left hallway from the main hall on the base floor (walk opposite of the kitchen door). At the end, there is a Mimicry Marcus. If you are having difficulty facing him head on, you can observe this video for how to skirt around him, and hit him while he turns. I have seen some guides claim you can bring in a partner with a knife, this doesn't work! You can only use one person.
Weapons + Checklist
"This Is How You Recycle": Create a Molotov Cocktail.
Combine empty bottles and gasoline cans.
"Custom To Bust 'Em": Create a Custom Handgun.
As noted in the "Apprentice Of Unlocking" achievement, the only missable key is the one for the custom handgun parts. Combine them with Rebecca or Billy's default handgun.
"I Could Shoot, You Know": Obtain all weapons.
You do not have to kill enemies with each weapon, just having them in your inventory/equipping them for a moment will count.
WEAPONS CHECKLIST:
[ ] Rebecca's Handgun - Default. Has a red-brown-ish lining and black middle.
[ ] Billy's Handgun - Default. Has silver lining and wood look.
[ ] Knife 1# - Billy default.
[ ] Knife 2# - Train, cabin 102.
[ ] Hunting Gun - Train, cabin 101.
[ ] Shotgun - Training Facility, storage room. Same room you get the black statue piece.
[ ] Grenade Launcher - Art room, place with two Plague Crawlers and the locked water door.
[ ] Magnum - Cable car, on dead body.
[ ] Molotov Cocktail - See "This Is How You Recycle".
[ ] Rebecca's Custom Handgun - Combine her gun with the custom parts.
[ ] Billy's Custom Handgun - Combine his gun with the custom parts.
[ ] Sub-Machinegun - Complete the game with rank A+.
[ ] Rocket Launcher - Complete the game with rank S.
[ ] Magnum Revolver - Complete Leech Hunter with rank B+.
If you've done the handgun parts before, and do not remember whose you modified (since there is no title to differentiate them) save them for last, and make a save before combining them to see which one you missed. Don't worry too much about it, since as you will see, you'll be replaying a few times.
Playthroughs
Using your file with the Leech Hunter bonus weapons to gun-ho your way thru these will save you years of your lifespan. LH may be a bit tedious, but will save you even more tedious runs of inventory management.
"S Is For S.T.A.R.S.": Finish the game with rank S.
The only requirement is to beat the game in under 3 hours and 30 minutes. ..Thats it! You can save as much as you want, heal as much as you want, and use infinite weapons. Don't stress too much about this requirement, as you do the below challenges, you'll become quickly acquainted on sprinting thru the game. My time usually ended up somewhere around 2 hours.
"Who's Got The Herb?": Finish the game without combining herbs.
"Allergic To First Aid Spray": Finish the game without using a First-Aid Spray.
"This Is Serious Business": Finish the game without using a recovery item (including Green Chemicals).
"Save Your Prayers": Finish the game without saving.
Again, sounds intimidating, but becomes a joke when you have an infinite magnum. If you are intimidated, you can do a "no heal" run where you save, and then a "no save" run where you heal. I was unfortunately forced to do it this way, as Rebecca got grabbed by Mimicry Marcus during the Laboratory section where she exits the downstairs area into that hallway. With her in caution, I made the decision to heal and did the "no heal" run after.
"That's Officer Chambers To You": Defeat all bosses except Centurion using Rebecca.
If you want to save time, you may want to do this using the "yes heal no save"/"no heal yes save" method, as Becky can be a little squishy. This achievement does not work like the files/herbs/weapons, where you can do it across multiple runs. It must be done in a single playthrough. Make sure Billy is set to idle, he cannot do a lick of damage! Here is a list of the following bosses, and how to make sure Rebecca fights them:
[ ] Stinger - Train boss, make sure you send Billy up the ladder so he gets stuck in the room.
[ ] Centurion - Only Billy can fight Centurion.
[ ] Infected Bat - Have Billy stand on the plate outside the Church, and send Rebecca in.
[ ] Proto Tyrant 1# - Only Rebecca can fight him.
[ ] Proto Tyrant 2# - In the treatment plant, make sure Rebecca is the only one going down the elevator. Also, something funny I found, but make sure Billy isn't standing on the elevator, as he will come down too even if you have him set to "solo".
[ ] Queen Leech 1#, 2# - Now we move onto the finale, where you can't have Billy sitting in another room. Make sure hes unequipped before entering, so he doesn't accidentally fire.
[ ] Queen Leech 3# - The game will automatically swap you to Billy after a cutscene, and you can only finish her off with him. ..Talk about stealing all the glory.
"From Zero To Hero": Finish the game on Hard difficulty.
We finally reach (what I assume is yours too) the end. The training wheels come off here. ..I used a video guide :P I had to improvise at some parts (such as storing healing items, since the OP did not use them.) but I personally found this guide easiest and fastest to follow. You can also consult Optinoob's video, if you prefer commentary.
Wesker Mode
Another fun bonus mode for completing the game, found in the "Extras" menu. You can also use your Leech Hunter bonuses here! WM is always set to Normal difficulty. I placed WM here at the bottom, as there is no gameplay advantage for completing it.
"20/20 Vision": Kill 50 enemies with the Death Stare at full charge.
I'm going to be honest, I forgot how to trigger his stare since I finished this run really fast. But I believe you need to unequip normal weapons, and hold down the aim button so he begins charging, and then release once its red (full).
"Welcome To Team Wesker": Put on Team Wesker costume.
For completing WM, you get Rebecca's outfit to wear in the main campaign. Simply load or create a save, and swap her into it.
