We present 2 patients who underwent orthotopic heart transplantation for end-stage Chagas' cardiomyopathy. Despite immunosuppressive therapy, postoperative prophylaxis with nifurtimox appeared to prevent Trypanosoma cruzi reactivation. Neither patient has shown signs of Chagas' myocarditis, and both are clinically well 12 and 72 months after transplantation. The successful outcome of our patients suggests that heart transplantation is a reasonable therapeutic option in patients with end-stage Chagas' cardiomyopathy.