"Fires .44 Magnum rounds. An extremely powerful handgun, not to mention one of Barry's favorites."
The Anaconda is obtained only by Jill Valentine, and only if Barry is killed. The Anaconda is capable of inflicting massive amounts of damage, in fact, being the only weapon that can take out the T-002 Tyrant's first form in a single shot, and its limiter-removed variant in two. However, there are no extra .44 rounds available to the player, causing the Anaconda to become useless once all six bullets are fired.
Barry also used this Magnum on his rescue mission in the events of Revelations 2 along with his Samurai Edge and an Assault rifle. However, the magnum looks quite different from its model in Resident Evil (2002) and Resident Evil 5. The base model for the gun this time around is a Smith & Wesson 500, rather than the Colt Python/Anaconda from previous games. The barrel has the same modification as in previous games, but as evident by the 5 round cylinder seen in cutscenes and the S&W logo on the side of the gun. This is still the same weapon as used by Barry in previous games, but a different model. Players can use this weapon in Raid Mode as well. Ammo is still scarce in the Campaign, but not so in Raid Mode.
- It also kills other bosses in one shot including Yawn, Crimson Head Prototype 1 and Plant 42.
- Barry uses the weapon twice in Resident Evil 5, in his two "instant death attacks": Gun Bash and Miranda Rights. The weapon doesn't need to be reloaded.