Risk factors for death after heart transplantation were identified by analyzing the total primary heart transplantation experience (n = 911) among 25 institutions from January 1, 1990, through June 30, 1991. Overall actuarial survival was 93% at 1 month and 84% at 12 months. The hazard function for death was highest early after heart transplantation and fell rapidly over the first 6 months, with a gradually declining hazard thereafter. The two most common causes of death were infection (n = 29) and early graft failure (n = 28), accounting for 45% of the overall deaths. By multivariable analysis, risk factors for death during the study period included very young recipient age (p = 0.004), advanced age (p = 0.009), ventilator support at time of transplantation (p = 0.09), abnormal renal function (p = 0.1), lower pretransplantation cardiac output (p = 0.009), higher pulmonary vascular resistance in children (p = 0.006), longer donor ischemic time (p = 0.001), older donor age (p = 0.001), and donor and recipient not both blood type O (p = 0.009). The recipient age effect was greatest in patients under 5 years of age (1-year survival rate 68% versus 85% for all others, p = 0.002). Patients aged 60 years and older had a 1-year survival rate of 81%. Patients who were ventilator dependent at transplantation fared especially poorly, with a 3-month survival rate of 65%. Transplantation of a blood group O heart into a non-O recipient had a somewhat lower 1-year survival rate than did blood group O into an O recipient (82% versus 88%, p = 0.06). The adverse effect of a longer ischemic time was most notable after 4 hours (1-month survival rate 71% for more than 4 hours versus 85% for less than 4 hours, p = 0.0003). Inference: These multiinstitutional-derived risk factors for early-term death after heart transplantation may help improve patient and donor selection and focus further scientific investigations to increase the safety of heart transplantation.