Investigators with the HIV Outpatient Study (HOPS) sought to evaluate the association of bone fracture with mortality. This analysis included 6,763 participants contributing 51,443 person-years of follow-up: 504 (7.5%) had incident fracture recorded. Of the 504 fractures, 135 (26.8%) were major osteoporotic fractures. At baseline, participants who later experienced incident fracture were older and more likely to: be a current or prior smoker, have 7 or more alcoholic beverages per week at HOPS cohort entry, have been diagnosed with HIV for longer duration, have an AIDS diagnosis, be ART experienced, and have lower nadir CD4. Incident fracture was associated with a nearly 50% increase in risk of all-cause mortality. Subset analysis of participants who experienced fracture revealed a mortality rate of 2.97 (CI 0.86-2.05) per 100 PY for persons with major osteoporotic fractures. All-cause mortality was significantly associated with having any of the following chronic conditions: cardiovascular disease, chronic kidney disease, HCV coinfection, pulmonary disease, or history of non-AIDS cancer.