Resident Evil: Gaiden is the first and only Resident Evil game for the Game Boy Color, Development began after the port of the original Resident Evil to the system was canceled. A notable change in perspective, movement, and combat were made to bring the series to a handheld system. Later games in the series make no mention, or even directly contradict, the events of Resident Evil: Gaiden, and have proven the story of this game is non canon.
Resident Evil: Gaiden is played from two perspectives. Movement is controlled from a top-down perspective while combat is in a first person perspective. Combat is initiated by moving a d-pad controlled reticule over an on screen, or when a zombie comes in contact with the character. Once combat begins, a bar with a slider appears at the bottom of the screen, representing the player's aim. Enemies are damaged when the player attacks while the slider moves over the bar representing the enemy, and timing is key. The center of the enemy's bar can be attacked for critical damage. The player controls up to three characters at once, with the ability to switch characters and enter the item screen without pausing the battle.
Following the destruction of Raccoon City, an organization is formed whose mission is to put an end to Umbrella. Leon S. Kennedy is sent to investigate the existence of a new Bio-Organic Weapon (B.O.W.) that is said to be on the ocean liner, Starlight. Contact with Leon is lost, and Barry Burton is sent in to find Leon and eliminate the B.O.W.
Soon after arrival, Barry discovers the passengers have become zombies. A scream let's Barry know that at least one person is still alive. The scream comes from a girl named Lucia, who is being chased by the B.O.W. Barry tries to protect her, but the B.O.W. manages to capture her.
Barry finds Leon, catches him up with what's going on, and they go after the girl and manage to rescue her. Soon after, an explosion threatens to sink the ship. Leon and Lucia go off to activate the sprinkler system, while Barry attempts to communicate with headquarters for an air lift.
After successfully activating the sprinklers, Leon and Lucia find their way back to Barry. However, as they reunite, the two of them overhear Barry making a deal to sell Lucia to Umbrella. Leon confronts him, and Barry pulls a gun on Leon and takes Lucia captive.
Barry takes Lucia to an Umbrella submarine that is waiting for him. Before he can go after her, another explosion rocks the ship, and Leon runs to attempt to repair the damage. He finds the B.O.W., fights it off, but learns there is no hope for the ship.
On board, the captain tells him that there is a parasite in Lucia that will turn her into a new B.O.W. in ten days. Barry reveals his deal was simply a deception to get on board the submarine, and he forces the submarines surgeons to remove the parasite. Unfortunately, the parasite escapes, and infects the inhabitants of the sub, and Barry and Lucia are forced to flee back to the sinking ship.
The two of them find what appears to be Leon, but it turns out the new B.O.W.s are shape-shifters. They escape and find the real Leon in the engine room. They return to the top deck to confront the B.O.W., and it pulls Lucia into the sea. Barry rescues her, but then another Lucia appears. Lucia cuts her hand, revealing red blood, as opposed to the green blood of the B.O.W., and the three of them make a final stand.
The three of them are rescued, and Lucia is offered a place to live in Barry's home. The final scene shows green blood dripping from Leon's neck.