We examined risk factors for avascular bone necrosis (AVN) particularly focusing o the question of whether antiretroviral treatment (ART) is associated with the emergence of osteonecrosis. After 11 years of following the entire cohort, 26 patients were found to have AVN. Compared to 260 concurrent HIV-infected controls, at risk when cases were diagnosed, patients with AVN had lower CD4 cell count nadirs (median 86.5 versus 137.5 cells/microl, p = 0.010) and suffered significantly more often from Pneumocystis pneumonia, cerebral toxoplasmosis, CMV retinitis, and atypical mycobacteriosis and had a significantly higher body mass index than controls. Duration of ART before AVN was not significantly different between cases and controls (2.92 versus 2.17 years, p = 0.30). In conclusion, AVN could not be attributed to time on antiretroviral treatment, but patients with AVN had histories of more severe immunosuppression and a higher body mass index than controls.