Although prevention of metabolic bone disease is a principal component of management of end-stage renal disease, the clinical epidemiology of long-bone fractures is not completely understood. Hospital discharge claims from 1994 through 1999 for 7159 subjects in the Dialysis Morbidity and Mortality Study were used to quantify incidence and risk factors of long-bone fractures and to test the hypothesis that long-bone fractures are associated with cardiovascular and infectious events and death in patients receiving hemodialysis. The incidence of long-bone fractures was 16.93 per 1000 patient-years, with the femoral neck being the most common site (59.8%); multivariate analysis revealed greater risk with older age, female gender, diabetes, more years receiving dialysis, and cardiovascular disease, and lower risk with African American race, increasing body mass index, parathyroid hormone values in the fourth quintile (227.1-538.0 pg/mL), and renal transplantation during followup. Postfracture mortality rates were 522.57 per 1000 patient years (versus 215.35 in the overall population). Time-dependent analysis suggested the adverse prognosis of long-bone fractures was related to subsequent congestive heart failure, stroke, pulmonary embolism, pneumonia, and septicemia. Long-bone fractures are common in patients receiving dialysis; their adverse prognostic implications may be linked to major cardiovascular and infectious events.