Donor cause of death may be a risk factor for early mortality after heart transplantation, but its effect on medium-term survival is uncertain. By means of a national prospective database, we investigated the influence of donor cause of death on survival to 3 years in 1254 adult recipients of cadaveric heart transplantation between July 1995 and June 2002. Donor cause of death was categorized a priori as vascular and tumor (group V, n = 739), trauma (group T, n = 407), hypoxic (group H, n = 82), and infective causes (group I, n = 26). Risk factors for early (30-day), late (30-day to 3-year), and overall mortality were identified with Cox regression. Group V donors were more likely to be older ( P < .001) and female ( P < .001). There were 297 deaths in the 3-year period, and the unadjusted 3-year survivals varied significantly (group V 73%, group T 79%, group H 85%, group I 80%, P = .01). Cox analysis identified donor age, organ ischemia time, recipient creatinine clearance, recipient diagnosis, peripheral vascular disease, ventilation, diabetes, and donor-recipient size mismatch as risk factors for early, late, or overall mortality ( P < .10). After adjustment for these factors, donor cause of death was no longer a significant predictor of recipient death (early death P = .36, late death P = .79, overall mortality P = .37). We confirmed that there is an apparent association between cause of donor death and posttransplantation survival, but this was not maintained after adjustment for confounding variables. Donor cause of death therefore should not influence donor organ acceptance or donor-recipient matching and does not identify marginal donors.