Frank West & his pupil,Vicky Chu investigates the destruction of Raccoon City. After they are taken by S.T.A.R.S.,Fontana & her men begun killing members to find Frank ever since the zombies attack the mall. Rebecca Chambers helped Frank & Vicky escape by taking them out. She tells them about distress call going on.
Fontana hires Calder to hunt them down. Later,Frank,Vicky,& Rebecca found a dead man before being attacked by a mutated leech,sent by the Queen Leech. They manage to escape and begun making a discovery at the lab. They learned that the mutated leeches were created by the scientist & co-founder of Umbrella Corporation,James Marcus,who was assassinated on the orders of the other co-founder,Oswell Spencer.
They are ambushed and captured by Calder & his men. They are suddenly attacked by the Queen Leech,who kills Fontana while Calder fled. The Queen Leech reveals to be the re-animated James Marcus,who was brought back by the mutated leech.
Frank & the others and made their way to the train. The Queen Leech appears and transform into its monster appearance. They fought against as the Military open fire,causing the bridge to be destroyed. The car that Frank & the Queen Leech are on dangles. Frank made his way up & shoot the hook,sending the monster and the fuel crashing down. As they leave,They are both picked up by the S.T.A.R.S. Helicopter.
Mid-Credits:
Calder was found by Wesker,who tells him that he has a job for him.