The aim of the study was to identify the main determinants of grassroots project success among HIV/AIDS NGOs operating in Rakai, Uganda. It was a cross-sectional study using face-to-face interviews in a mixed-methods approach among community members and NGOs involved in providing HIV/AIDS and related health services. The study found that the success of grassroots projects of HIV/AIDS NGOs essentially relies on adequate financial resources, competent human resources, strong organizational leadership, and NGO networking. These data suggest that to increase grassroots project success, HIV and AIDS NGOs in Rakai need to improve not only the budget base and human capacities but as well decision-making processes, organizational vision, mission and strategies, gender allocation in staffing, and beneficiary involvement.