AMP! (Arts-based, Multiple component, Peer-education) is an HIV intervention developed for high school adolescents. AMP! uses interactive theater-based scenarios developed by trained college undergraduates to deliver messages addressing HIV/STI prevention strategies, healthy relationships, and stigma reduction towards people living with HIV/AIDS. We used a pre-test/post-test, control group study design to simultaneously assess intervention effect on ninth grade students in an urban county in California (N = 159) and a suburban county in North Carolina (N = 317). In each location, the control group received standard health education curricula delivered by teachers; the intervention group received AMP! in addition to standard health education curricula. Structural equation modeling was used to determine intervention effects. The post-test sample was 46 % male, 90 % self-identified as heterosexual, 32 % reported receiving free or reduced lunch, and 49 % White. Structural models indicated that participation in AMP! predicted higher scores on HIV knowledge (p = 0.05), HIV awareness (p = 0.01), and HIV attitudes (p = 0.05) at the post-test. Latent means comparison analyses revealed post-test scores were significantly higher than pre-test scores on HIV knowledge (p = 0.001), HIV awareness (p = 0.001), and HIV attitudes (p = 0.001). Further analyses indicated that scores rose for both groups, but the post-test scores of intervention participants were significantly higher than controls (HIV knowledge (p = 0.01), HIV awareness (p = 0.01), and HIV attitudes (p = 0.05)). Thus, AMP!'s theater-based approach shows promise for addressing multiple adolescent risk factors and attitudes concerning HIV in school settings.