BACKGROUND: Low bone mineral density in HIV-infected patients is an increasingly recognized clinical problem. The aim of this study was to determine the incidence, prevalence, and risk factors for development of low trauma or fragility fractures in an HIV-infected population. METHODS: A 1:2 matched case-control study was performed of HIV-infected patients attending the Alfred Hospital between 1998 and 2009. Controls were matched on gender, age, and duration of HIV infection. RESULTS: The overall fracture incidence rate was 0.53 per 100 person-years [95% confidence interval (CI): 0.43 to 0.65] and period prevalence of 3.34 per 100 patients (95% CI: 2.66 to 4.13). There were 73 low trauma fractures in 61 patients. Patients were predominantly male (89%) with a mean age of 49.8 years. Independent risk factors for fragility fracture were a CD4 cell count <200 cells per microliter odds ratio (OR): 4.91 (95% CI: 1.78 to 13.57, P = 0.002), corticosteroids OR: 8.96 (95% CI: 1.55 to 51.88, P = 0.014) and anti-epileptic medications OR: 8.88 (95% CI: 1.75 to 44.97, P = 0.008). There were no significant associations between HIV viremia (P = 0.18), use of or class of antiretroviral medication, and risk of fracture. Eighty-eight percent of patients with fracture had established osteopenia or osteoporosis. CONCLUSION: This is the largest clinical study to date of fragility fractures occurring in an HIV-infected population. The study found that risk of fracture was strongly associated with a low CD4 cell count, use of corticosteroids, and anti-epileptic medications. There were no associations between fracture risk and viral load, use of class, or duration of antiretroviral agent.