The Veterans Health Administration (VHA) sees approximately equal to 17,000 human immunodeficiency virus (HIV)-infected patients each year, which makes it the largest provider of HIV care in the United States. HIV causes chronic progressive disease that leads to early death. Newer combination antiretro viral treatments are effective but expensive and difficult to use. The HIV Quality Enhancement Research Initiative (HIV-QUERI) uses the QUERI process to identify high-risk and high-volume populations (step 1), which includes those already under VHA care for HIV, those who do not know of their infection, and those at risk for HIV. In identifying best practices (step 2), the HIV-QUERI will benefit greatly from existing guidelines for the care of established HIV infection, but gaps in knowledge regarding adherence to medication regimens and cost-effective screening are large. To identify existing practice patterns (step 3), the HIV-QUERI will develop a clean analytic data set based on Immunology Case Registry files and expand it through a survey of veterans. Interventions to improve care (step 4) will include national, regional, and site-specific feedback on performance relative to quality standards, as well as patient-level and provider-level interventions to improve adherence and support medical decision-making. To document that best practices improve outcomes and quality of life (steps 5 and 6), HIV-QUERI will track indicators on an ongoing basis by use of the Immunology Case Registry database and possible future waves of the survey. In addition, we will require that these issues be addressed in evaluations of HIV-QUERI interventions. In the present article, we present these steps within a framework and plan.