In an attempt to identify the factors that influence survival after heterotopic heart transplantation, 42 consecutive recipients of heterotopic heart transplant were reviewed. Preoperative pulmonary artery pressures, pulmonary vascular resistance, and donor age significantly differed between hospital survivors and nonsurvivors. Postoperative survival analysis between pairs of groups of patients divided by each of these variables disclosed a significant difference, which confirmed the effects of these variables on survival. Evolution of pulmonary hemodynamics was compared between patients with preoperative pulmonary artery diastolic pressure greater than 25 mm Hg (pulmonary hypertension; n = 22) or less than 25 mm Hg (nonpulmonary hypertension; n = 20). Despite marked differences in preoperative pulmonary hemodynamics, pulmonary artery pressures were dramatically reduced immediately after transplantation, and pulmonary vascular resistance diminished to upper normal limits at 10 days when there were no longer differences in pulmonary vascular resistance between the two groups. Immediate deaths were related to left ventricular failure, and the incidence was similar between the groups. Despite such normalization of pulmonary hemodynamics, patients with preoperative pulmonary hypertension experienced more frequent ventricular fibrillation, required longer respiratory support, and developed lethal pulmonary or systemic infection, which resulted in a 32% (7/22) hospital survival rate compared with 90% (18/20) in patients without pulmonary hypertension. Despite the dramatic improvement in pulmonary hemodynamics, heterotopic heart failed to demonstrate the expected advantages because of frequent pulmonary complications and infection, which resulted in failure to improve the prognosis of patients with preoperative pulmonary hypertension.