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The literature contains few descriptions of the infective organisms and diagnostic issues associated with musculoskeletal infections in patients with HIV. We retrospectively reviewed 19 patients with HIV treated at our musculoskeletal infection ward for septic arthritis. The mean CD4 count was 154/mm3 (range, 7-482/mm3), and 11 patients had a CD4 count < 200/mm3 and were diagnosed with AIDS. The most common pathogen (six patients) was oxacillin-resistant Staphylococcus aureus. Mycobacterial infections occurred in three patients but no fungal pathogens were identified. Septic arthritis was monoarticular in 14 patients and involved the knee in eight patients, the hip in three patients, and the wrist in three patients. Five patients presented with polyarticular septic arthritis. All mycobacterial infections and four of the five polyarticular infections occurred in patients with a CD4 count < 200/mm3. Patients with CD4 count < 200/mm3 had a lower joint fluid WBC count compared to patients with a CD4 count > 200/mm3 (40,500 vs 69,000/mm3). Oxacillin-resistant Staphylococcus aureus was the most common pathogen. A high index of suspicion for Mycobacterium. tuberculosis arthritis and polyarticular septic arthritis is necessary in patients with HIV and a CD4 count < 200/mm3.Level of Evidence: Level IV, diagnostic study. See Guidelines for Authors for a complete description of Levels of Evidence.