This study evaluated Girlfriends, a behavioral HIV intervention, developed for male-to-female transgender persons, for whom there are few scientifically evaluated prevention programs. The Girlfriends intervention included four group-level sessions. We used a single group, pre-post test design to assess changes in sexual risk behaviors at 3-month follow-up. We enrolled 63 transgender women into the study. Forty-six percent were Hispanic and 35% were African American. Three months after the intervention, participants had fewer sexual partners (p = .043) and were less likely to have any unprotected anal intercourse (UAI) with male exchange partners (p = .013) and unprotected sex at last vaginal or anal sex episode with female and male partners (p = .039). The findings of this study are promising. We observed behavioral effects among a largely ethnic minority sample of transgender women. Replication with a larger sample and a control group is needed.