To evaluate the prevalence and risk factors for low bone mineral density (BMD) in persons co-infected with HIV and Hepatitis C.HIV/HCV co-infected study participants (n=179) were recruited into a prospective cohort and underwent dual-energy X-ray absorptiometry (DXA) within 1year of a liver biopsy. Fibrosis staging was evaluated according to the METAVIR system. Osteoporosis was defined as a T-score ⩽−2.5. Z-scores at the total hip, femoral neck, and lumbar spine were used as the primary outcome variables to assess the association between degree of liver disease, HIV-related variables, and BMD.The population was 65% male, 85% Black with mean age 50.3years. The prevalence of osteoporosis either at the total hip, femoral neck, or lumbar spine was 28%, with 5% having osteoporosis of the total hip, 6% at the femoral neck, 25% at the spine. The mean Z-scores (standard deviation) were −0.42 (1.01) at the total hip, −0.16 (1.05) at the femoral neck, and −0.82 (1.55) at the lumbar spine. In multivariable models, controlled HIV replication (HIV RNA <400 copies/ml vs. ⩾400 copies/ml) was associated with lower Z-scores (mean±standard error) at the total hip (−0.44±0.17, p=0.01), femoral neck (−0.59±0.18, p=0.001), and the spine (−0.98±0.27, p=0.0005). There was no association between degree of liver fibrosis and Z-score.Osteoporosis was very common in this population of predominately African-American HIV/HCV co-infected patients, particularly at the spine. Lower BMD was associated with controlled HIV replication, but not liver disease severity.