Young persons are disproportionately affected by the impact of HIV in Nigeria. This paper presents findings from an evaluation of a national youth HIV prevention program designed to determine the effects of HIV prevention intervention (HPI) on Youths on Compulsory National Service (YoCNS) and Adolescents in Secondary Schools (AiSS). Data were collected from 229 YoCNS who received training on HIV prevention and 231 of their counterparts who did not. Among AiSS, data were collected from 909 respondents who were trained as peer educators and among 1005 students who were not. Data were collected in six states namely Akwa-Ibom, Enugu, Gombe, Kaduna, Plateau and Osun using a questionnaire that explored knowledge on HIV and sexual behavior and supplemented by focus group discussions and in-depth interviews. Results show that both youths and students who received HPI reported superior knowledge on HIV/AIDS than their counterparts who did not. Students in the intervention sites also reported fewer numbers of multiple sexual partners (9.7%) compared to those in the comparison sites (15.4%). The qualitative data shows that the project had positive effects on both youths and students who received the intervention. Given these positive outcomes, it is recommended that the project should not only be sustained but expanded to reach adolescents who are out of school.