Continuity mistake: It was briefly stated in the second film that the T-Virus was created by Dr. Ashford to cure his daughter Angela and that the Red and White Queens were based on her. This movie contradicts that by suggesting that Dr. Marcus created the T-Virus to cure his daughter Alicia, and that the Red/White Queens were modeled after her. While the rest of the movie stays true to the continuity of the previous films, this rather obvious ret-con is still a major continuity gaff.
Plot hole: At the beginning the Red Queen said that the last human settlement will fall in 48 hours unless Alice releases the anti-virus, however when Alice does release the anti-virus (a few seconds before the timer ends) she says it will take years for it to reach around all the corners of the globe, this does not make sense and implies that the last human settlement will fall anyway.
Continuity mistake: There is a scene of Alice being dragged by a line behind Isaacs' tank ahead of a horde of zombies. There is no other line next to running Alice. When she climbs upon the tank to attack the guard, another line with torn hands is seen being dragged on the road, where Alice was dragged. (00:21:15 - 00:23:45)Bunch Son
Trivia: The film's production was quite troubled. A crewmember named Ricardo Cornelius was killed in a freak accident when he was crushed by a Humvee and a stuntwoman named Olivia Jackson was severely injured, with her face being "de-gloved" and sustaining may injuries and fractures which resulted in the loss of her right arm. Thankfully she survived and made a full recovery and the doctors were able to surgically mend her face and other injuries.
Trivia: While the film had the lowest domestic gross of the series ($26 million in comparison to the $40-$60 million each other film grossed), it was somewhat ironically also the highest grossing film of the franchise internationally, and as a result also ended up being the highest grossing film of the series worldwide, earning $312 million against a $40 million budget. It serves as a rare example of a film that is a flop in domestic markets while still technically being a resounding success.
Alicia Marcus: I still own 50% of this company.
Dr. Isaacs: And what do you intend to do with that?
Alicia Marcus: You are co-owner of this corporation, but Wesker... Wesker is still an employee.
Wesker: I don't have to take your orders. My loyalties are with him.
Alicia Marcus: I know. Albert Wesker, you're fired.