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There is debate over the types of physicians who should treat patients with complex chronic medical conditions such as human immunodeficiency virus (HIV) infection. We sought to assess the relationship between specialty training and expertise and the quality of care delivered to patients with HIV infection.We selected random samples of HIV-infected patients receiving care at 64 Ryan White CARE (Comprehensive AIDS Resources Emergency) Act–funded clinics throughout the country and their primary HIV physicians for an observational cohort study in which quality-of-care measures were assessed by medical record review.We studied 5247 patients linked to 177 physicians who responded to a survey. Fifty-eight percent of the physicians were general medicine physicians (“generalists”) and 42% were infectious diseases specialists. Sixty-three percent of the generalists (37% overall) considered themselves expert in HIV care. In hierarchical logistic regression models that controlled for patient characteristics, infectious diseases physicians and expert generalists had similar performance. In contrast, nonexpert generalists delivered lower quality care. More than 80% of the appropriate patients being cared for by infectious diseases physicians and expert generalists were receiving highly active antiretroviral therapy, compared with 73% of appropriate patients of nonexpert generalists (P<.001). Physicians with fewer than 20 patients with active HIV had fewer appropriate patients on highly active antiretroviral therapy (73% vs 82% of physicians with ≥20 such patients, P = .04) and saw patients less frequently.These findings extend previous work by examining a range of quality-of-care measures and suggest that generalists with appropriate experience and expertise in HIV care can provide high-quality care to patients with this complex chronic illness.