Background: In Uganda’s HIV prevention strategy religious institutions are encouraged to deliver HIV prevention messages to the general public and to integrate HIV prevention into faith-based activities such as worship, funerals and marriage ceremonies. However, there is limited data on the relationship between religiosity and HIV prevalence. Objectives: The main objective was to assess the association between religiosity, HIV-risk behaviors and HIV prevalence. Methods: A case-control study was done among Muslim and Christian youth. Cases were defined as HIV positive youth and controls were HIV negative youth. Respondents were interviewed and then tested for HIV. A religiosity index was constructed to assess the association between religiosity, HIV-risk behaviors and HIV infections. Results: Higher levels of religiosity were significantly associated with abstaining from sex, avoiding drinking alcohol and avoiding narcotics. Higher levels of religiosity were also associated with lower HIV-infections. HIV infections were significantly associated with low religiosity, having one or both parents dead, and having multiple sexual partners. Conclusions: Religiosity appears to have an important role in HIV prevention among many Ugandans. These should be encouraged and made to feel proud of using religiosity in their HIV prevention efforts. Their numbers should also be increased. Religious leaders should be energized by the study findings and they should be supported to take the lead in the efforts of using religiosity for HIV prevention. All Ugandans should use the power of God within each of them for HIV prevention in line with their motto: “For God and my country”. Religiosity for HIV prevention is readily available, accessible and affordable to the majority of Ugandans. This option should be supported by all stakeholders including government, non-governmental organizations, faith-based organizations and external support agencies, by mobilizing appropriate human, technical and financial resources to accelerate its implementation.