Few studies have tested schoolwide interventions to reduce sexual risk behavior, and none have demonstrated significant schoolwide effects. This study evaluates the schoolwide effects of Safer Choices, a multicomponent, behavioral theory-based HIV, STD, and pregnancy prevention program, on risk behavior, school climate, and psychosocial variables. Twenty urban high schools were randomized, and cross-sectional samples of classes were surveyed at baseline, the end of intervention (19 months after baseline), and 31 months afterbaseline. At 19 months, the program had a positive effect on the frequency of sex without a condom. At 31 months, students in Safer Choices schools reported having sexual intercourse without a condom with fewer partners. The program positively affected psychosocial variables and school climate for HIV/STD and pregnancy prevention. The program did not influence the prevalence of recent sexual intercourse. Schoolwide changes in condomuse demonstrated that aschool-based program can reduce the sexual risk behavior of adolescents.