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Adolescent girls throughout the globe are particularly vulnerable to HIV infection. In the U.S., sexually-active, adolescent girls in urban settings are at elevated risk for HIV. The purpose of this study was to describe a theoreticallydriven, HIV prevention intervention tailored for adolescent girls and evaluate its effectiveness in reducing sexually-risky behaviors. Sexually-active urban adolescent girls (n=738) recruited in a mid-size, northeastern U.S. city were recruited for a randomized controlled trial and participated in a theory-based, sexual risk reduction intervention or a structurally-equivalent health promotion control group. Preferred sexual risk-reduction strategies were collected using ACASI at baseline, then at 3, 6 and 12-months post-intervention. The manualized interventions included four small group sessions and two booster sessions all of which included information, motivational and behavioral skill constructs. Facilitators were trained in motivational interviewing and incorporated this technique throughout the sessions. Relative to girls in the control group, girls receiving the sexual risk-reduction intervention were more likely to increase the number of sexual-risk reduction strategies at post-intervention; however, girls in the control group also increased the number of strategies used though not at the same rate. Theory-based, HIV interventions tailored to adolescent girls can help increase sexual risk-reduction behaviors and provide girls with a menu of options to employ. Due to the manualized structure of this randomized controlled trial, the intervention could be modified to meet the needs of adolescent girls throughout the world.Trial Registration: This study is registered at ClinicalTrials.gov (NCT 00161343).