PURPOSE: This study is part of a larger evaluation of a multilevel, multistrategy federal program to reduce high school students' risk for HIV/sexually transmitted infection and unintended pregnancy. Local education agencies supported schools in implementing three strategies: delivering exemplary sexual health education, increasing student access to quality sexual health services, and enhancing safe and supportive school environments (SSE). We examined how levels of school implementation of these strategies moderated program effects on targeted student outcomes. METHODS: The Youth Risk Behavior Survey was implemented in participating local education agencies in 2015 and 2017 to assess student behaviors and experiences, whereas the School Health Profiles surveys assessed school policies and practices in 2014 and 2016. We used these surveys to measure student-level outcomes and school-level program delivery, respectively, which were analyzed using multilevel modeling in a difference-in-differences framework. RESULTS: Levels of SSE implementation significantly moderated program effects on multiple student outcomes, including ever having sex, having four or more lifetime sexual partners, being sexually active, using hormonal birth control, dual use of a condom and hormonal birth control, ever being forced to have sex, missing school because of safety concerns, and lifetime and current marijuana use. However, we found few moderating effects of exemplary sexual health education and sexual health services dosage. DISCUSSION: We found a significant relationship between incremental increases in implementation of activities to increase the safety and supportiveness of school environments and enhanced program effects in improving multiple student health outcomes. These findings suggest that school implementation of SSE activities contributed to intended program effects.