In this study, we assessed whether peer education is an effective method of HIV/AIDS awareness, in terms of knowledge, misconception and behavior, among adolescents in the rural area of Nigeria. A comparative case series (n = 250), cross-sectional structured survey (n = 135) and focus group discussions (n = 80) were undertaken among adolescents. In both the case series and structured survey, a questionnaire was used which addresses the following issues: socio-demography, knowledge on transmission and prevention of HIV/AIDS, accessibility to different sources of HIV/AIDS information, stigmatization and sexual behavior. Binary logistic regression was applied to compare responses from the peer-educated and not peer-educated populations. The model was adjusted for confounders. We demonstrated increased knowledge and decreased misconception and sexual risk behavior in adolescents receiving peer education as compared to adolescents not receiving peer education. These differences are apparent both over time (2005-2007) and cross-sectional (2007). In conclusion, peer education in rural areas can be effective in HIV/AIDS prevention. Knowledge and behavior can be influenced positively.