Objective: To evaluate the effectiveness of Safe Thinking and Affect Regulation (STAR), a 14-session HIV-prevention program for adolescents at alternative/therapeutic schools. Because these youth frequently have difficulties with emotions and cognitions, it was designed to improve sexuality-specific affect management and cognitive monitoring, as well as HIV-related knowledge and attitudes. It was hypothesized that STAR would lead to a decrease in sexual risk and improved HIV knowledge and attitudes. Method: Fourteen schools were randomly assigned by year either to the STAR intervention or a brief educational program. Schools received the alternate intervention the following year. A total of 185 adolescents in 29 cohorts (groups) participated in the interventions. Assessment of sexual behavior, knowledge and attitudes with audio computer-assisted self-interviews occurred at 3, 6, and 9 months post intervention. Results: Hierarchical linear model (HLM) analyses found that adolescents in the STAR intervention reported a significantly greater decrease (p less than 0.05) in the Sexual Risk Index than youth in the control group over the 6 months post intervention and similar improvements in the HIV Knowledge Scale and the Condom Use Self Efficacy Scale. There were no group differences between 6 and 9 months post intervention. Conclusions: This STAR intervention for youth in alternative schools was associated with decreased sexual risk for 6 months after the intervention. These data suggest that intervention strategies that target cognitions and affect within a sexual context might be usefully applied to improving sexual behavior but may need to be reinforced over time. Clinical trial registration information--HIV, Abuse, and Psychiatric Disorders Among Youth; http://clinicaltrials.gov; NCT00603369. (Contains 5 tables and 1 figure.)