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Forty-three consecutive patients who were being treated with digitalis, angiotensin converting enzyme inhibitors, and diuretics were evaluated for orthotopic heart transplantation. After right heart catheterization in patients with more than 3 Wood units or with a mean pulmonary artery pressure higher than 30 mm Hg (n = 13; group 1), prostaglandin E1 (PGE1) therapy was initiated at a dosage of 5 ng/kg/min and was increased stepwise (mean maintenance dosage, 35 ng/kg/min) until side effects (joint pain, digital edema) occurred. After 6 days of PGE1 administration, dosage decreased stepwise. One week after PGE1 was stopped, right heart recatheterization was performed, and the patients were listed on the waiting list. Hemodynamic data significantly improved in PGE1-treated patients. Patients without pulmonary hypertension (group 2, n = 30) were put directly on the waiting list. No oversized or local donor was required for transplantation. Eight of 13 patients in group 1 underwent transplantation. The other five patients died while on the waiting list. In group 2, 15 patients underwent transplantation, and 15 patients died while on the waiting list. A prolonged mean survival time on the waiting list (6.0 versus 3.1 months, p < 0.005) was noticed in group 1. PGE1 was administered after orthotopic heart transplantation whenever indicated; no death was related to right ventricular failure in group 1. The results after orthotopic heart transplantation in patients treated with PGE1 were comparable to the control group. PGE1 therapy enabled us to perform orthotopic heart transplantation on patients with pulmonary hypertension at a comparable risk with normal heart transplant recipients.