The Samurai Edge makes an appearance in Resident Evil 5. It is seen used by Albert Wesker during his fight with Chris. He draws it out on Chris during the fight on the aircraft. He points it to Chris' head and says a few lines, before getting interrupted by Sheva stabbing him in the forearm with her knife. After more fighting, the Samurai Edge is shot out of Weskers hand by Sheva. It is presumably lost shortly after the aircraft crashes into a Volcano.
The Samurai Edge is only usable in Mercenaries and Mercenaries Reunion Mode. There are two versions of the weapon in Mercenaries, Wesker's Samurai Edge and Barry's Samurai Edge. Wesker's has 400 firepower but no special ability, while Barry's has 340 firepower and can pierce through multiple enemies. Wesker's Samurai Edge has a capacity of 15, Barry's has a capacity of 30. Both versions of the weapon can be acquired in the campaign by external means, but curiously, Barry's Samurai Edge will always result in an extremely low accuracy score at the end of a chapter. This is because Barry's Samurai Edge has the unique feature of shot properties resetting after piercing an enemy, allowing for the possibility of a piercing critical but also meaning shots that don't hit multiple enemies count as missed shots.