OBJECTIVES: Osteoporosis is characterized by low bone mass and increased fracture risk. Increased mortality rates have been documented following fractures, particularly hip and vertebral. Our aim was to compare short-term and long-term mortality rates following an incident fracture in men and women at different sites (hip, wrist, spine, humerus and others). METHODS: We identified a population-based cohort of men and women with non-traumatic incident fractures between 1986 and 2006 within the hospital, physician and pharmacy administrative database repository of the Province of Manitoba, Canada. The cohort-entry date was the date of a first fracture (index fracture) after age 50 years. Two matched controls from the same databases were identified for each case. Crude and adjusted mortality rates for each fracture site were computed separately for men and women. Secular trends in fracture site-specific mortality rates over the study period were tested using generalized linear models. RESULTS: We identified 23,514 index fractures in men and 52,897 in women. The crude mortality rates were consistently higher in men compared to women. Highest first year mortality rates were noted after hip (women 20.1% vs. men 33.6%) followed by spine fractures (13.9% vs. 15.8%), with lower mortality rates after humerus (7.4% vs. 15.3%), wrist (3.4% vs. 5.3%) and other fractures (9.2% vs. 11.0%). Similar rankings by fracture site were seen for year five mortality: hip fractures (women 53.1% vs. men 66.7%) followed by spine (38.4% vs. 43.1%), humerus (26.6% vs. 41.2%), wrist (15.7% vs. 21.2%) and other fractures (26.5% vs. 29.3%). Post-fracture mortality rates were generally stable over the study period. CONCLUSIONS: Fractures at all sites are associated with significant mortality rates, particularly in men. Better understanding of factors associated with increased post-fracture mortality will inform the development of practice guidelines and improved clinical outcomes.