Unlock PRL 412
Clear Leon’s Story on Professional difficulty to unlock the PRL 412 weapon. It has two settings — stun and kill (just like Star Trek) which you may determine by holding or tapping the fire button. It has infinite ammunition.

Unlock Thompson Gun
To unlock the Thompson Submachinegun, clear Leon’s story mode (any difficulty) and complete Ada’s story mode (Separate Ways). Purchase it from the Roma merchant when playing a new game plus.

Ada can also have the weapon available for her own side-story mission (Assignment Ada) simply simply clearing that particular mode once. Again, speak with the Roma merchant to access it.

Unlockable Costumes And Modes
Clear the main game (any difficulty) to unlock:

* Professional Difficulty
* Mercenaries Challenge
* Separate Ways Mini-Campaign
* Alternate costumes for Leon, Ashley, and Ada Wong

Unlockable: Maria
You must get 3000 or more points in Game D.

Hint: Exclusive Weapon Powers
Each weapon has a special “exclusive power” when all of its stats are custom tuned to the maximum:

HANDGUN- 5 times more of a chance of critacal head shot
PUNISHER- Each bullet can penetrate up to five bodies.
RED 9- Increases firepower to 6.5
BLACKTRAIL- Increases firepower to 3.4
MATILDA- Increases magazine capacity to 100.
SHOTGUN- Increases the effective damage range of the gun.
RIOTGUN- Increases firepower to 10.0 and 8.0 at long range
STRIKER- Increases magazine capacity to 100.
RIFLE- Increases firepower to 30.0
SEMIAUTO RIFLE- Decreases firing speed to 0.42 seconds.
BROKEN BUTTERFLY- Increases damage to 50.0
KILLER7- No exclusive power!
TMP- Increases firepower to 1.8
Minethrower - Adds homing ability to mines

Unlockable PS2 Costumes
Clear the Separate Ways mode to unlock more costumes for Leon and Ashley.

Easter Egg: Gangster Pose
In order to do this trick you need to first pick Leon’s gangster outfit, and then equip the Chicago Typewriter machinegun. Reload the machinegun a few times in a row and Leon will pose.
Submitted by maartyrr
Hint - Keep The Special Rocket Launcher
Without using a Gameshark (or similar device), you can keep the Special Launcher Ada throws down during the final fight. Simply unlock the P.R.L. weapon unlocked by completing Professional difficulty mode to waste Saddler. When Ada tosses out the Special Launcher, get it, and finish Saddler with the P.R.L. When you begin the game again, you will have Special Launcher (note still one shot).

Easter Egg
Leon may sit in the red throne after the laser hallway by inspecting it. Nothing interesting occurs, but it makes for an interesting screenshot.

Originally from IGN