The final installment of the "Blade" trilogy, "Blade: Trinity," is often considered the worst of the original three films. After "Blade" and "Blade 2" were both well-received, "Trinity" was savaged by critics over David S. Goyer's direction as well as the script (via Rotten Tomatoes), with Jamie Russell of BBC describing the movie as "sometimes bloody, sometimes bloody awful." Production difficulties also could've contributed to this, as costar Patton Oswalt said that Wesley Snipes and Goyer had trouble working together for various reasons (via The A.V. Club).

Lyonne appears in the film as Sommerfield, a member of a team of vampire hunters called the Nightstalkers who has a young daughter. Sommerfield is the scientist of the group and works to research the vampire genome, eventually creating an anti-vamp virus called Daystar. However, she ends up getting killed by Drake (Dominic Purcell) near the end of the film, during an attack on the hideout.

Looking back, Lyonne openly dislikes her performance, but she's able to laugh about it too. On "The Late Late Show With James Corden," reunited with "Blade: Trinity" star Jessica Biel, Lyonne joked that she knew she hadn't given a great performance when Kris Kristofferson told her on set that she reminded him of Janis Joplin. "That's when I knew I'd blown it," she told the audience.