Thirty years later, the saved child has become the vampire hunter Blade. Whistler, his ally, have been waging a secret war against vampires with Blade. As Karen, a hemetologist, is now "marked" by the bite of a vampire, both he and Blade tell her to leave the city.

Upon returning to her apartment, Karen is attacked by a policeman, who is a vampire. Blade uses information from him to locate an archive of vampire history. Later, Blade injects himself with a special serum that prevents him from turning into a vampire. However, the serum is beginning to lose its effectiveness due to overuse.

Later, Karen discovers that a special medication, EDTA, explodes when combined with vampire blood. Frost and his men attack the hideout, infect Whistler, and abduct Karen. When Blade returns, he helps Whistler commit suicide and arms himself with special syringes filled with EDTA.

In the end, Blade confronts Frost. During their fight, Blade injects Frost with all of the syringes, causing his body to inflate and explode, killing him.