With the exception of story achievements, all other achievements in this game can be missed. Although some are quite hard to miss, it is still possible to do so. If your goal is to achieve 100% completion, don't worry about achievements during your first playthrough, as multiple runs will be necessary to attain them all.
Story Achievements
The following story-related achievements cannot be missed.
Harpoon Hurler
Grilled Big Cheese
Wave Goodbye, Right Hand
No Thanks, Bro!
You Used to Be a Good Guy
You’re Small Time!
Combat / Upgrade Achievements
Knife Basics
Parry an enemy with the knife
Use the knife to deflect an enemy attack.
My Preferred Place
Upgrade a weapon
At the Merchant, use Ptas to upgrade a weapon.
A Masterpiece
Get the exclusive upgrade for a weapon
After fully upgrading a weapon, a new, expensive upgrade will become available for purchase.
Gun Fanatic
Obtain all weapons
The majority of weapons can be bought from the Merchant, while certain weapons will become available during NG+ playthroughs as a reward for accomplishing specific feats. You can find a comprehensive list of all weapons in the order they appear in the game in the "All Collectables in Order of Appearance" section of this guide.
Shield Your Eyes
Defeat 3 enemies at once with a Flash Grenade
In order to do this you must shoot the heads of 3 enemies causing the parasite to emerge from their necks. While this can sometimes be unpredictable, it's possible to force it by fighting the armored enemies, as they always have a parasite.
Never Heard It Coming
Defeat a Garrador using only Knives
A Garrador is the blind armored enemy. You have to kill it completely using only knives. Sprint to alert it and it will charge you. He should then get stuck in a wall allowing for some free hits.
Two Bugs, One Stone
Kill 3 parasites inside a Regenerator with a single bullet
Not quite sure what weapon will be best for this achievement at the moment. Will update when more information becomes available.
You Talk Too Much!
Throw a grenade into Ramón Salazar’s mouth
During this boss fight, throw a grenade into Ramón Salazar’s mouth.
Overkill
Use a cannon to defeat a zealot
Hope You Like Thrill Rides!
Make it through both minecart sections in the underground tunnel without taking damage
This might just take a few attempts. If you take damage, just load a previous checkpoint.
Capacity Compliance
Reach the top of the clock tower without the lift stopping once
To obtain this, you need to defeat enemies rapidly as they jump onto the lift. If too many enemies accumulate on the lift, it will come to a halt.
Smooth Escape
Escape on the water scooter without taking any damage
At the end of the game, complete the water scooter section without taking damage.
Talk About Near-Death Experience!
Rescue Ashley as she’s being carried away by the enemy
If an enemy gets too close to Ashley, they will try to grab her and take her away. To prevent this, shoot the enemy in the leg, which will cause them to release her.
Clockwork Castellan Achievements
To find all clockwork castellan and other collectibles, check out our guide to find all collectibles in Resident Evil 4 Remake.
Revolt Against the Revolting
Destroy a Clockwork Castellan
Revolution Wind-Up
Destroy all Clockwork Castellans
Run Specific Achievements
These achievements stack - you can complete the game in Professional and it would unlock all the achievements for previous difficulties.
Promising Agent
Complete the main story on Standard mode or higher
Mission Accomplished S+!
Complete the main story on Standard mode with an S+ rank
Proficient Agent
Complete the main story on Hardcore mode or higher
S+ Rank Investigator
Complete the main story on Hardcore mode with an S+ rank
Peerless Agent
Complete the main story on Professional mode with an S+ rank
Sprinter
Complete the main story within 8 hours
Easier on NG+ and on lower difficulties.
Frugalist
Complete the main story without using a recovery item
Minimalist
Complete the main story using only Knives and Handguns [Including specific battles]
Silent Stranger
Complete the main story without talking to the Merchant once
It seems possible to earn the Frugalist, Minimalist, and Silent Strange achievements by playing through NG+ with a fully upgraded pistol. In this case, there would be no need to interact with the Merchant and it would be possible to reload a checkpoint if you sustain damage. However, it's worth noting that certain bosses may prove challenging, so it may be necessary to attempt the Frugalist achievement separately.
Misc Achievements
Nice One, Stranger!
Complete a request for the Merchant
The Merchant has requests you can complete throughout the game for rewards. Complete 1 of them for this achievement.
Jack of All Trades
Complete all requests from the Merchant
The Merchant has 19 requests you can complete throughout the game for rewards. Complete all of them for this achievement. All are listed above in the "All Collectables in Order of Appearance" section of this guide.
Astute Appraiser
Sell a single Treasure for at least 100000 Ptas
As you progress, you'll get more and more valuable items you can sell to the Merchant.
Bandit
Obtain all Treasures indicated on the Village Treasure Map in a single playthrough
You can purchase the treasure maps from the merchant and all valuable items will be marked on your map.
Raider
Obtain all Treasures indicated on the Castle Treasure Map in a single playthrough
You can purchase the treasure maps from the merchant and all valuable items will be marked on your map.
Burglar
Obtain all Treasures indicated on the Island Treasure Map in a single playthrough
You can purchase the treasure maps from the merchant
and all valuable items will be marked on your map.
Amateur Shooter
Complete a game at the shooting range
You'll be able to play this minigame after making it to the Castle. Simply complete 1 round with any amount of points.
Trick Shot
Shoot through and destroy 5 targets at the shooting range with a single shot
Real Deadeye
Earn an S-rank in all games at the shooting range
Get an S-rank in each game at the shooting range.
>>> Read more: 5 Tips And Tricks To Beat Resident Evil 4 Remake Easily