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Nurse practitioners (NPs) and physician assistants (PAs) are primary care providers for patients with HIV in some clinics, but little is known about the quality of care that they provide.To compare the quality of care provided by NPs and PAs with that provided by physicians.Cross-sectional analysis.68 HIV care sites, funded by Ryan White Comprehensive AIDS Resources Emergency (CARE) Act Title III, in 30 different states.The authors surveyed 243 clinicians (177 physicians and 66 NPs and PAs) and reviewed medical records of 6651 persons with HIV or AIDS.8 quality-of-care measures assessed by medical record review.After adjustments for patient characteristics, 6 of the 8 quality measures did not statistically significantly differ between NPs and PAs and either infectious disease specialists or generalist HIV experts. Adjusted rates of purified protein derivative testing and Papanicolaou smears were statistically significantly higher for NPs and PAs (0.63 and 0.71, respectively) than for infectious disease specialists (0.53 [P = 0.007] and 0.56 [P = 0.001], respectively) or generalist HIV experts (0.47 [P < 0.001] and 0.62 [P = 0.025], respectively). Nurse practitioners and PAs had statistically significantly higher performance scores than generalist non-HIV experts on 6 of the 8 quality measures.These results may not be generalizable to care settings where on-site physician HIV experts are not accessible or to measures of more complex clinical processes.For the measures examined, the quality of HIV care provided by NPs and PAs was similar to that of physician HIV experts and generally better than physician non-HIV experts. Nurse practitioners and PAs can provide high-quality care for persons with HIV. Preconditions for this level of performance include high levels of experience, focus on a single condition, and either participation in teams or other easy access to physicians and other clinicians with HIV expertise.