HIV prevention programming is increasingly taking place in school settings, which provide an expansive population of young people and offer immense potential for making a large and much-needed impact in the lives of this target group. The Presidential Initiative on AIDS Strategy for Communication to Youth (PIASCY) is an ambitious, school-based programme that has sought to address the HIV/AIDS epidemic in Uganda in a holistic manner since 2002, targeting young people, school personnel, parents, and the wider community. A formative evaluation was conducted by the African Population and Health Research Center (APHRC) in February 2009 to provide an understanding of: the extent to which PIASCY is achieving its planned goals and objectives (e.g., increased capacity to deliver learning resources and materials, increased skills and knowledge of chief actors, and promotion of stigma-free school environments); the strengths and limitations of the design, organisational structure, and rollout of PIASCY; the lessons learned and best practices for continued rollout of the programme; the unintended consequences of the development and implementation of the programme; and the sustainability issues facing the programme's continued implementation. The study findings highlight the positive elements of the programme that can serve as a foundation as PIASCY is rolled out to post-primary institutions, as well as challenges that need to be addressed in preparation for this process.