Disclaimer: Puzzle answers in Resident Evil 4 Remake may vary slightly depending on difficulty level. Most solutions are consistent across Standard and Assisted modes, but Hardcore and Professional modes can feature different puzzle answers, most notably for specific locks and visual-based puzzles. Always double-check puzzle clues in-game when playing on higher difficulties.


Puzzle Solution Differences

Similar to Resident Evil 2 Remake (and possibly Resident Evil 3 Remake), puzzle solutions in Resident Evil 4 Remake can change depending on the difficulty.
I'll go over which puzzles stay the same across difficulties, and which ones are altered.

Village Chief's House:
This puzzle does not change across difficulties.
The cabinet solution is always: Crop → Pig → Baby.
The marble door puzzle remains the same — simply spin the marble until the Plagas symbol overlaps.

Lake Heads Puzzles:
These puzzles are also unchanged across all difficulties.
Numbering the heads clockwise starting from the two-symbol head as #1:

Cave near the chicken farm: 4, 6, 7

Cave near the first boat: 2, 5, 8

Hexagon Puzzle:
This one varies based on difficulty:

Assisted/Standard: Rotate the Left group once, then the Top group once.

Hardcore/Professional: Rotate the Right group twice, Left group twice, Top group once.

Church Stained Glass Puzzle:
The solution remains consistent across all difficulties.
Simply rotate each color panel until they form the Plagas symbol at the center.

Sword/Knight Puzzle (after Garrador):
The puzzle logic remains the same, but on Hardcore/Professional there are additional gongs to shoot.
Shoot the gongs matching the symbols on the gate, collect all four swords, and place them into the murals left to right in this order:
Iron Sword → Golden Sword → Bloodied Sword → Rusted Sword.

Lithographic Stone Puzzle:
Stone locations slightly change depending on difficulty, but the solution remains the same.
All stones are still found within the room.
Correct placement (starting from the top, going clockwise):

Shield with Square Border
Sword with Square Border
Armor with Hexagon Border
Helmet with Hexagon Border

(Note: You can flip the lithograph stones — a step many players miss.)

Dissection Room:
Assisted/Standard: https://www.powerpyx.com/wp-content/uploads/resident-evil-4-remake-collectible-219-2.jpg
Hardcore/Professional: https://www.powerpyx.com/wp-content/uploads/resident-evil-4-remake-electric-lock-terminal-1.jpg

Freezer:
Assisted/Standard: https://www.powerpyx.com/wp-content/uploads/resident-evil-4-remake-collectible-221-2.jpg
Hardcore/Professional: https://www.powerpyx.com/wp-content/uploads/resident-evil-4-remake-electric-lock-terminal-2.jpg

Waste Disposal:
Assisted/Standard: https://www.powerpyx.com/wp-content/uploads/resident-evil-4-remake-collectible-241-2.jpg
Hardcore/Professional: https://www.powerpyx.com/wp-content/uploads/resident-evil-4-remake-electric-lock-terminal-3.jpg

Applies to all difficulties. Most weapons are found in fixed locations or bought from the Merchant. Some upgrades or special versions are unlocked after completing certain challenges.

• Flash Grenades, Hand Grenades, and Heavy Grenades:
  
• Found throughout the world or crafted from materials.

Notes:

• Most standard weapons can be purchased directly from the Merchant.
  
• Some powerful weapons (like the Red9 or LE 5) must be found through exploration.
  
• Bonus weapons (Handcannon, Chicago Sweeper, Infinite Rocket Launcher) require challenge completion or New Game+.

Unlocks Overview:

Professional/Pinstripe Costume:
Complete Chapter 16 on any difficulty.

Primal Knife:
Destroy all 16 Clockwork Castellans (1 per chapter).
Some can be backtracked to later if missed.
(Link to an accurate location guide will be added later.)

Wolf Tail (Hidden Challenge):
Complete the game on Assisted difficulty with an S+ rank.

Sunglasses (Round) / Foam Mask / Flight Cap:
Complete the game on Standard difficulty or higher.

Glasses (Square) / Iron Helmet / Knitted Hat:
Complete the game on Standard difficulty or higher with an A rank.

Deer Antlers:
Complete the game on Standard difficulty with an S+ rank.

Glasses (Round) / Flight Helmet / Surgical Mask:
Complete the game on Hardcore difficulty or higher.

Ashley’s Armor:
Complete the game on Hardcore difficulty or higher with an A rank.

Chicken Hat:
Complete the game on Hardcore difficulty with an S+ rank.

Gas Mask:
Complete the game on Professional difficulty.

Handcannon:
Complete a fresh Professional run (no bonus weapons allowed).
No rank requirement. Costumes and accessories that provide gameplay bonuses are still allowed.

Chicago Sweeper:
Complete the game on Professional difficulty with an A rank.

Cat Ears:
Complete the game on Professional difficulty with an S+ rank.

Infinite Rocket Launcher:
Unlocked for purchase from the Merchant in New Game+.
Costs 2,000,000 pesetas.
(Not automatically unlocked like other items.)

Unlock Effects:

Wolf Tail:
Greatly increases melee attack damage (approximately +20%).

Deer Antlers:
Significantly boosts knife damage (approximately +20%).

Ashley’s Armor:
Makes Ashley completely immune to damage, even during her solo section.
(Warning: If she’s grabbed while you’re transitioning through double doors, it can still cause a game over.)

Chicken Hat:
Greatly reduces damage taken (around 40% reduction).
(This stacks with body armor bonuses.)

Cat Ears:
Grants infinite ammo for all guns.
(You must still manually reload, but ammo is not consumed from your inventory.)

Handcannon / Chicago Sweeper / Primal Knife:
Extremely powerful weapons when fully upgraded.
Their exclusive upgrades provide infinite ammo (Handcannon, Sweeper) or infinite durability (Primal Knife) without the need to reload.
(Bonus: Equipping the Handcannon or Chicago Sweeper while wearing the Pinstripe costume triggers a unique reload animation.)

Obtaining Ranks

Here are the rank requirements for each difficulty:
[link]https://gamefaqs.gamespot.com/a/user_image/5/9/0/AAOb2IAAEWdu.jpg[/link]

A and S ranks can be earned in New Game+ runs, but S+ ranks must be achieved on a fresh new game (no NG+).
For Professional difficulty, achieving S+ also requires completing the game with 15 saves or fewer.

Note: Once unlocked, the Handcannon, Primal Knife, and Chicago Sweeper will always appear in your typewriter storage across all save files — including fresh new games.
These weapons can be freely used during S+ runs without disqualifying you from earning the rank.

I hope this guide helped you rescue "baby eagle" from the Los Illuminados!

Throughout my time earning 10+ Resident Evil platinum trophies — including 7 on console — I’ve written several personal guides to help myself along the way.
I'm happy to finally share some of that knowledge here, and I hope it makes your experience a little smoother.