Background: Vertically oriented global health initiatives (GHIs) addressing the HIV/AIDS epidemic, including the President's Emergency Plan for AIDS Relief (PEPFAR), have successfully contributed to reducing HIV/AIDS related morbidity and mortality. However, there is still debate about whether these disease-specific programs have improved or harmed health systems overall, especially with respect to non-HIV health needs. Methods: As part of a larger evaluation of PEPFAR's effects on the health system between 2005-2011, we collected qualitative and quantitative data through semi-structured interviews with District Health Officers (DHOs) from all 112 districts in Uganda. We asked DHOs to share their perceptions about the ways in which HIV programs (largely PEPFAR in the Ugandan context) had helped and harmed the health system. We then identified key themes among their responses using qualitative content analysis. Results: Ugandan DHOs said PEPFAR had generally helped the health system by improving training, integrating HIV and non-HIV care, and directly providing resources. To a lesser extent, DHOs said PEPFAR caused the health system to focus too narrowly on HIV/AIDS, increased workload for already overburdened staff, and encouraged doctors to leave public sector jobs for higher-paid positions with HIV/AIDS programs. Conclusion: Health system leaders in Uganda at the district level were appreciative of resources aimed at HIV they could often apply for broader purposes. As HIV infection becomes a chronic disease requiring strong health systems to manage sustained patient care over time, Uganda's weak health systems will require broad infrastructure improvements inconsistent with narrow vertical health programming.