You need to reload manual saves to catch anything you miss - there is no free play after the story and no chapter select.
Three playthroughs are needed for 100% (on each difficulty) - but 4 or more may be needed for the collectibles as well.
Difficulty DOES affect achievements
4 missable achievements (plus 18 unknown)
Sign in with Steam or Xbox to track your progress, and:
Escape from uptown Raccoon City.
Craft an item.
combine items to craft things. You'll find items throughout the game and can do this at any point. It'll be an easy early unlock.
Expand your inventory.
Improve a weapon.
Destroy a Charlie Doll.
Defeat Nemesis on the rooftop.
Defeat two enemies with a single shot.
You'll probably just get this naturally through the course of play. Don't worry about trying to set up for it.
Cause Nemesis to relinquish an item.
Make it out of Downtown Raccoon City.
Defeat zombie Brad.
When playing as Carlos, the first enemy to fight is Brad. Kill him.
If you don't, you'll see him again later in the police station in the safety deposit room.
He's pretty tough...
Leave the clock tower plaza.
Withstand the zombie siege.
Follow Nicholai deeper underground.
Defeat Stage 2 Nemesis.
Defeat Stage 3 Nemesis.
Place all jewels in the clock tower monument.
Escape from Jill's apartment building.
This should be the first unmissable story achievement you get - but on Steam its glitched at launch and seems to not unlock for hardly anybody.
Collect all weapons in the campaign.
Complete the game on "Standard" or higher.
Unlock all safes, lockers, strongboxes, and pickable locks.
Complete the game on "Hardcore" or higher.
Gather the fuses in the warehouse within 5 minutes.
Complete the game with an S rank.
Complete the game in under 2 hours of play time.
Complete the game using 1 or fewer recovery items.
You can't use more than one "herbs", "mixed herbs" or "sprays".
You can still use recovery coins - which you can get from the shop after completing the story. These help a lot - and they don't count as healing items.
This is therefore best done on your 2nd or subsequent playthrough.
Read all story files.
Destroy all Charlie dolls.
Complete the game without opening the item box.
Complete the game on "Nightmare" or higher.
Complete the game on “Nightmare” or higher.
Complete the game on "Inferno."
Complete the game on "Inferno" difficulty
Complete the game with an S rank on "Inferno."