OBJECTIVE To study clinical and laboratory factors in patients with systemic lupus erythematosus (SLE) to identify subgroups at extraordinary risk for developing osteonecrosis. METHODS 31 of 103 (30%) patients with SLE had developed osteonecrosis. Patients were studied to identify clinical characteristics that differentiated patients with and without osteonecrosis. Subjects were studied to determine whether and to what degree factors leading to thrombophilia (anticardiolipin antibodies, aCL) or hypofibrinolysis [lipoprotein(a)] are associated with osteonecrosis. RESULTS Clinically, the patients with osteonecrosis had significant increases in Cushingoid body habitus, thrombophlebitis, vasculitis, cigarette smoking, and preeclampsia. Highest prednisone dose was positively associated with osteonecrosis. Although IgG aCL were also found to be associated with osteonecrosis, particularly in the white patients with SLE, lipoprotein(a) levels were not increased in either the white or black patients. CONCLUSIONS Maximal prednisone doses, changes in body habitus in response to corticosteroid therapy, IgG aCL levels, and clinical evidence of venous thrombosis and vasculitis were associated with osteonecrosis in patients with SLE.