Background: Historically, patients with AL amyloidosis and overt congestive heart failure have had an ominous prognosis with median survival of approximately 6 months. Methods: Between 1994 and 2005, 11 patients underwent sequential orthotopic heart transplantation (HT) followed by autologous peripheral blood stem cell transplantation (SCT) for treatment of AL amyloidosis. Patients were accepted for this approach if they had heart-dominant AL with minimal/no other organ impairment and no evidence of multiple myeloma. Conditioning chemotherapy consisted of melphalan 200 mg/m2 (6 patients) or melphalan 140 mg/m2 (5 patients). Results: Two patients died of complications from the SCT (18% transplant-related mortality). Nine patients survived both the HT and the SCT. Three patients subsequently died from progressive amyloidosis at 66, 56.7 and 55 months after SCT. The 1- and 5-year survival for HT was 82% and 65%. The median survival was 76 months from HT and 57 months from SCT. Conclusions: These data suggest that aggressive treatment of the underlying plasma cell clone after HT may improve long-term outcomes in patients with cardiac amyloid. HT followed by SCT is feasible and offers the possibility of remission for carefully selected patients with cardiac amyloidosis.