Objective: The study aims to assess the association between bone mineral density (BMD) and frailty in a cohort of HIV-infected patients. Design: A cross-sectional study in an HIV outpatient unit where nearly 1000 patients are monitored. Methods: Study participants undergoing bone densitometry were proposed an evaluation of frailty using criteria of the Cardiovascular Health Study (CHS) and the Study of Osteoporotic Fractures (SOF). Frailty markers were weight-loss, self-reported exhaustion , physical activity, grip strength, chair stands, and slow gait. Patients' characteristics were collected from an electronic medical record. Associations of frailty with BMD and osteoporosis were tested using multivariate linear and logit regression models, respectively. Results: In total, 175 HIV-infected patients, 121 (69.14%) men, were analyzed. Prevalence of frailty markers, osteopenia, and osteoporosis were comparable among sexes. Despite a younger age, spinal and femoral neck BMD were lower in women (P < 0.05). Linear regression model adjusting by age, duration of HIV follow-up, BMI, smoking status, osteoarthritis, osteoporosis treatment, and the age at menopause showed a negative association of spinal and femoral BMD with frailty according to SOF criteria in women (P < 0.05). In men, SOF-defined frailty was associated with osteoporosis (odds ratio 28.79; 95% confidence interval 2.15-386.4) in a model adjusting for age, duration of HIV follow-up, CD4 þ nadir, CD4 þ T-cell count, tobacco consumption, exposure to tenofovir (TDF) and protease inhibitors. No significant associations were found between BMD and CHS-defined frailty. Conclusion: Our study shows that frailty according to SOF criteria is associated with low spinal BMD values in female and osteoporosis in male HIV-infected patients.