OBJECTIVES: Although the prevalence of low bone mineral density (BMD) and bone fractures are increased among HIV-infected adults compared with the general population, no study has yet characterized their causal association in the context of HIV infection.    METHODS: We analyzed available dual energy X-ray absorptiometry (DEXA) values of the hip (left femoral neck) and clinical data collected prospectively during 2004-2012 from two CDC-sponsored HIV cohort studies, the HOPS and the SUN Study. We assessed factors associated with low BMD (osteopenia or osteoporosis, defined by T-scores of -1.0 to >-2.5, and ≤ -2.5, respectively), using the Jochkheere-Terpstra test for ordered alternatives for continuous variables and the Cochran-Armitage test for categorical variables. We analyzed the association of low BMD with subsequent incident fractures using Cox proportional hazards regression.  RESULTS: Among 1008 patients (median age 42 [interquartile range (IQR)35-48] years, 83% male, 67% non-Hispanic white, median CD4+ cell count [CD4] 408 cells/mm [IQR 254-598]), 36.3% (n=366) had osteopenia and 2.9% (n=29) osteoporosis.  During 5,032 person-years of observation after DEXA scanning, 95 incident fractures occurred, predominantly rib/sternum (n=18), hand (n=17), foot (n=15) and wrist (n=11). Low BMD was significantly (p<0.05) associated with age, lower nadir CD4, history of fracture, and male-male sex HIV transmission risk. In unadjusted analyses, age, current or prior tobacco smoking, hepatitis C co-infection, history of fracture, and low BMD (osteopenia or osteoporosis) were significantly associated with increased hazard of new fracture. In multivariable analyses, only osteoporosis (adjusted hazard ratio [aHR] 3.04, 95% confidence interval [CI] 1.47-6.30) and age (aHR 1.35 per 10 years, 95% CI 1.07-1.70) remained associated with incident fracture. CONCLUSIONS: In a large convenience sample of relatively young HIV-infected adults in the U.S., low baseline BMD and increasing age were strongly associated with elevated risk of incident fracture, highlighting the potential value of DEXA screening in this population.