Objective: The femoropopliteal vein (FPV) graft has been used extensively for large-caliber vascular reconstructions. To date, there have been no reports of anastomotic dehiscence or rupture leading to graft-associated hemorrhage (GAH). In the present report, we review our experience with GAH from FPV grafts to determine the incidence of this problem, to better understand the etiology, and to determine potential methods to prevent this complication. Methods: All patients undergoing arterial reconstructions with FPV grafts were entered into a registry that included demographics, operative details, complications, and follow-up information. Episodes of GAH that occurred during the period from 1990 to 2004 were studied to determine etiologic factors and outcomes. Results: During the study period, 574 FPV grafts were used for arterial reconstructions in 364 patients. GAH occurred in 11 patients (3%). Onset of GAH ranged from 1 hour to 180 days after operation. The mean blood transfusion requirement for GAH was 10 ± 4 units. In three patients, the etiology of GAH was purely technical, resulting in a slipped or "popped" tie from a large side branch. In eight patients, the etiology was due to graft disruption secondary to uncontrolled infection and failure of anastomotic healing. Most of these patients were being treated for aortic graft infection. Special risk factors for this complication included malnutrition, ongoing polymicrobial and fungal infections, immunocompromised state, active cancer, steroid treatment, and ongoing graft contamination from gastrointestinal or pharyngeal leaks. Outcomes included four deaths and one stroke. Conclusions: GAH is a serious complication with high morbidity, mortality, and transfusion requirements. Although technical problems are preventable, FPV grafts, like all biologic grafts, can develop disruption with GAH from ongoing infection, especially in severely immunocompromised patients who are malnourished and have poor healing ability. Strategies for prevention and alternative treatment modalities are appropriate in patients at high risk for GAH.