Abstract Objective The clinical features and outcomes of patients undergoing heart transplantation after a failed Fontan operation are still debated. The aim of this study was to retrospectively evaluate our experience in 14 patients undergoing heart transplantation after previous Fontan-type operations. Methods From 1990 to 2002, 14 patients underwent heart transplantation in our institution after a previous Fontan procedure. The mean age at the time of the Fontan operation and at transplantation was 7.3 ± 2.8 and 17.2 ± 6.3 years, respectively. The indication for transplantation was protein-losing enteropathy in 7 patients, arrhythmia with ventricular dysfunction in 5 patients, and heart failure in 2 patients. All patients received basic immunosuppressive therapy with cyclosporine (INN: ciclosporin) and azathioprine without induction therapy or maintenance steroids. Results Two hospital deaths occurred: one patient died on the fifth postoperative day of graft failure, and the second died on the 17th postoperative day after an acute neurologic event. Two patients died later, one 23 months after transplantation of acute rejection and the other after 90 months of chronic rejection and endocarditis. One patient underwent successful reintervention 2 years after heart transplantation for pulmonary vein obstruction. The 10 surviving patients are in New York Heart Association class I, with a mean follow-up of 64.5 ± 42 months. One of them was delivered of a healthy baby 5 years after transplantation. Patients with protein-losing enteropathy reached a normal protein level within a mean of 10 months (range, 6-18 months) after transplantation. Four patients required a temporary administration (3-6 months) of oral steroid therapy for recurrent rejection episodes. Currently, 7 patients are taking cyclosporine, and 3 are taking cyclosporine and azathioprine. The actuarial survival at 1, 5, and 10 years was 86% ± 9%, 77% ± 12%, and 62% ± 17%, respectively. Conclusion Heart transplantation is a good option for patients with a failing Fontan operation. We documented the reversibility of protein-losing enteropathy in all patients. No mortality caused by surgical complications was observed.