Resident Evil was followed by two sequels: Resident Evil: Apocalypse (2004) and Resident Evil: Extinction (2007). Anderson continued his involvement in the series, writing and producing the sequels, however, leaving directing to Alexander Witt and Russell Mulcahy.
The film begins in The Hive, a top-secret underground genetic research facility owned by the Umbrella Corporation located beneath Raccoon City. A man loads the T-Virus and its cure into a case, then tosses a vial of the virus inside a lab. Minutes later, the facility's security system kills everyone inside through various means. Elsewhere, Alice later awakens in the shower of an empty mansion with no recollection of her identity. As she explores the mansion she is confronted by a man, however the two are immediately seized by a group of commandos. The man, Matt Addison, reveals himself to be a police officer, but the commandos handcuff him regardless. The team opens a mirror-door to an underground train station, discovering Spence, another unconscious victim suffering amnesia. Alice recognizes Spence from a wedding photograph in the mansion, and looking at her wedding ring, she sees the inside of it reads: Property of the Umbrella Corporation.
The "One", as he was called, is the head of the commandos and explaines that Alice, Spence, and the commandos, are employees of the Umbrella Corporation, and it was the Umbrella Corporation that sent the commando team to investigate why the Hive's defensive computer, the Red Queen, killed all Umbrella staff. She was responsible for releasing a nerve gas in the mansion which has caused Alice and Spence's amnesias, but throughout the film Alice begins to have glimpses of her past. The crew find their way to the Queen's chamber; however, as the bulk of the team attempt to disable the Red Queen, they are trapped in the corridor leading to the Queen's Chamber and are torn apart by a laser grid. This leaves Alice, Spence, Kaplan, J.D., Rain and Matt as the only survivors. Alice and Kaplan shut the Queen down, but in doing so open the doors of the facility, releasing the undead staff and experiments from the laboratories in which they were imprisoned. Rain becomes infected after receiving multiple bite wounds, and a battle ensues in which Matt and Alice are separated and J.D. is killed. Alice discovers that Matt was not a police officer, and used the title as a cover in his goal to help take down the Umbrella Corporation. Matt, with the help of his sister, Lisa, attempts to smuggle a sample of the T-Virus, the cause of the zombies, but the two were unsuccessful. Matt believes this to be the fault of Lisa's contact, who supposedly betrayed her. Throughout the film Alice has flashbacks, showing herself as Lisa's contact, but Alice is not fully aware of her role in the events.
Soon, the survivors are once more united at the Queen's chamber and are forced to switch her back on for aid in an exit. Kaplan overrides the Queen's circuit-breaker, causing the next time she is disabled to be permanent, and the Red Queen somewhat agrees to aid the team. As Alice and the others try to escape through the maintenance tunnels, they are ambushed by zombies. Rain becomes severely injured and begins to weaken, while Kaplan is separated from the rest of the team and is assumed dead. On their way to the train, Alice remembers that an anti-virus exists that could cure the ailing Rain. However, arriving at the lab, they realize that the vials containing the T-Virus and anti-virus are gone. Spence, gaining his memory, is then shown as the person who released the virus. He points a gun at the survivors, and threatens them, trapping the others in the laboratory and making for the train where the case containing the anti-virus is. Before he can inject himself, however, he is killed by a Licker, a mutant-creature created by injecting the T-Virus directly into living tissue. The Queen offers to spare Alice and Matt's life if they kill Rain, who has been infected for the longest period of time. As the Licker attempts to bash through the lab window to get to them, the enraged Alice smashes the Queen's monitor, and there is suddenly a power-outage. The laboratory door opens to reveal Kaplan, who has permanently disabled the Red Queen.
The remaining four survivors hurry to get to the other end of the underground railway before it shuts down in a quarantine attempt. However, the Licker is on the train; it scratches Matt and kills Kaplan. Alice battles the Licker and Rain, who, despite being given the cure, has turned into a zombie. Matt and Alice emerge as the only survivors, and escape at the last moment when the doors close. Matt begins to suffer a mutation from an injury inflicted by the Licker, and the two are seized by Umbrella scientists. The scientists mention sending Matt to the "Nemesis Program"; a role detailed further in the film's sequel. Alice attempts to fend off the scientists, but is ultimately subdued. As the struggle fades to black, the words of one of the head scientists are heard, "We're reopening the Hive, I want to know what really went on down there. Just do it." Sometime later, Alice awakens at the Raccoon City Hospital, having gone through extensive testing and confined within a locked observation room. After escaping the room and wandering the hospital's empty halls, Alice exits the building to find Raccoon City abandoned with apparent signs of chaos everywhere. The headline of an old newspaper clearly exclaims "The dead walk!" Alice acquires a shotgun from a nearby police car, anticipating danger ahead, at which point the film ends.