This study examined the impact of two interventions delivered in rural communities and schools in Edo State, Nigeria designed to decrease youth vulnerability to HIV infection. The Ministry of Education approved Family Life and HIV Education (FLHE) programme delivered in Junior Secondary Schools and a community-based initiative to raise AIDS Competency of rural communities were evaluated using a clustered randomized control trial and mixed qualitative-quantitative methods. Ten schools were assigned to each of three research arms: FLHE programme only, FLHE and community programme, and control. Results demonstrated positive effects on rejection of myths, attitudes related to abstinence and use of condoms, and sexual activity. Confidence in these results is supported by both levels of statistical significance and consistency in patterns of results across different levels of schooling. Results support expansion of delivery of the FLHE programme and development of community-based initiatives as effective methods of reducing youth vulnerability to HIV infection.