In May 2006, Bill Kong announced that he was producing a live-action film adaptation of Blood: The Last Vampire, directed by Ronny Yu. Like the source anime, it would be primarily filmed in English rather than Japanese. Kong and Yu originally planned to finance the project themselves, but in November 2006, Production I.G officially consented to the film and began offering financial support. Rather than being paid a straight license, Production I.G will receive a percentage of all revenues generated by the film. Through ties to Manga Entertainment, the French company Pathe became the film's co-production company, joining the Hong Kong-based Edko. Yu was retained as its producer, but Chris Nahon took over as the film's director.
South Korean actress Jun Ji-hyun, who adopted the English screen name Gianna Jun for the release, plays the role of Saya.
Originally slated to be released worldwide in spring 2008, the film premiered in Japan on 29 May 2009, and was released in the United Kingdom on 26 June 2009. Sony Pictures Worldwide Acquisitions Group licensed the film for release in North America, where it was released to theaters by Samuel Goldwyn Films on 10 July 2009.
In early announcements, it was stated that the film would be set in 1948 at a United States Army camp in Tokyo, shortly after the conclusion of World War II during the American occupation of Japan. During production, the film was shifted to be set in the 1970s instead (the original setting for the anime).