Objectives: Despite findings suggesting that young adults are more concerned about experiencing an unplanned pregnancy or contracting a sexually transmitted infection (STI) than becoming human immunodeficiency virus (HIV) infected, no empirical work has investigated whether the specific focus of an intervention may be more or less efficacious at changing sexual behavior. Participants: Participants were 198 college students randomized to 1 of 4 conditions: pregnancy intervention, STI intervention, HIV intervention, or a control condition during 2008-2009. Methods: The authors compared the efficacy of 3 theory-based, sexual risk-reduction interventions that were exactly the same except for an exclusive focus on preventing pregnancy, STI, or HIV. Condom use and risky sexual behavior were assessed at baseline and 4-week and 8-week follow-up. Results: Participants exposed to the pregnancy or STI interventions reported greater condom use and less risky sexual behavior than those exposed to the HIV intervention. Conclusions: The focus of sexual risk-reduction interventions may lead to differential behavior change among young adults. (Contains 3 tables and 1 figure.)