Purpose: Adolescent females continue to face health consequences associated with risky sexual behaviors such as unintended pregnancies and sexually transmitted diseases. The purpose of this study was to investigate the efficacy of a gender-specific intervention targeted to early adolescent females. Method: This study used an intent to treat randomized clinical trial comparing a broad-based female empowerment curriculum with a dose-matched science and technology female leadership curriculum. The sample (N = 801) was recruited from schools and was implemented in community-based settings mostly in an after school context. Assessments were conducted at baseline, postintervention, 6-, and 18-month follow-up time periods. Results: Both groups in the study obtained good implementation and engagement. The average attendance rate was 81% of program sessions. There were significant differences between the two groups favoring the intervention group on measures of sexually transmitted disease knowledge and condom technical skills. On a measure of condom self-efficacy, there was a significant trend. At the postassessment, there was a significant difference on the intentions to reduce sexual risk behaviors. Both the intervention and control groups made gains on the self-assertive behavior scale. Conclusions: Gender-specific programs for early adolescent females can help reduce indicators that are related to sexual risk reduction. More long-term follow-up is needed to assess impact on sexual behaviors. Efforts directed at a younger population of females should continue to be researched for potential in reducing sexual risks.