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Despite calls for evidence-based HIV/STI prevention programs for youth aged 12 to 14 transitioning to adolescence, few effective programs exist. In a two-group intent-to-treat randomized trial in the Bronx, NY, 397 participants were randomly assigned to Project Prepared or an attention control, TEEN. Participants completed surveys at baseline, 6 months, and 12 months. Prepared had two components, an 11-session program and a 3-week internship. Content covered sexual risk behavior, social cognitions, gender norms, relationships, and resilience. TEEN built communication skills and had the same intensity and structure as Prepared but no sexual content. In both, boys and girls were trained together in mixed groups of ~ 11 teens. Primary outcomes were HIV knowledge, self-efficacy, condom outcome expectancy, and behavioral intentions. Secondary outcomes were relationship expectations and endorsement of risky gender norms. Generalized estimating equation analyses showed youth randomized to Prepared had significant improvements compared to TEEN at T2 in HIV knowledge, sexual self-efficacy, and outcome expectancy for condom use. At T3, there were significant differences favoring Prepared in outcome expectancy for condom use, sexual self-efficacy, and intention for partner communication about HIV/AIDS or STIs. Analyses by gender showed program effects in both boys (intention to talk to a partner about condom use, abstinence self-efficacy, sexual self-efficacy, and condom outcome expectancy) and girls (gender norms, and abstinence outcome expectancy). Prepared effectively reduced risk in young adolescents. ClinicalTrials.gov ID: NCT01880450, Protocol ID: 2008-551