Osteonecrosis, a disabling complication associated with antiretroviral therapy (ART) and human immunodeficiency virus (HIV) infection, has rarely been reported in an Asian population. After an observation of 3,250 person-years (PY), 11 of 967 (1.1%) HIV-infected patients at a median age of 34 years developed osteonecrosis involving the hip joints (incidence, 3.4 per 1,000 PY). Their median CD4+ lymphocyte count had increased from 35 cells/microL at the diagnosis of HIV infection to 297 cells/microL at the diagnosis of osteonecrosis. The crude rate of osteonecrosis increased from 0% in patients without exposure to ART to 2.6 and 1.7% in patients with exposure to nucleoside reverse transcriptase inhibitors (NRTIs) and who had undergone highly active antiretroviral therapy (HAART) for 5 years or longer, respectively (P=0.18 and 0.09, respectively). Among the patients receiving HAART, the estimated incidence of osteonecrosis was 4.2 per 1,000 PY. Patients with osteonecrosis had a longer duration of exposure to NRTIs (1,641 versus 1,264 days, P=0.26) and to HAART (1,603 versus 1,251 days, P=0.42), a higher serum triglyceride (median, 1,130 versus 351 mg/dL; P=0.09), and a higher proportion of lipodystrophy (81.8 versus 15.0%, P<0.0001). Our report suggests that osteonecrosis is a rare complication in HIV-infected patients with prolonged exposure to ART with resultant metabolic complications.