In Ig light chain (AL) amyloidosis, cardiac involvement is associated with worse prognosis and increased treatment-related complications. In this retrospective cohort study, we assessed survival, hematologic and cardiac responses to high-dose melphalan and auto-SCT (HDM/SCT) in patients with AL amyloidosis and cardiac involvement, stratified by cardiac biomarkers brain natriuretic peptide and Troponin I, analogous to the Mayo cardiac staging. Forty-seven patients underwent HDM/SCT based upon functional measures; six patients had modified cardiac stage I disease, seventeen had modified cardiac stage II disease and twenty-four had modified cardiac stage III disease. Treatment-related mortality was 4% for all patients and 8% for patients with stage III disease. Three-year survival was 88% and EFS was 47%; these did not differ by stage. By intention-to-treat analysis, 27% of patients achieved a hematologic complete response and 32% a very good partial response, of whom 70 and 45%, respectively, have not required additional therapy at 36 months. Cardiac response was achieved in 53% of patients. We conclude that with appropriate patient selection and a risk-adapted treatment approach, HDM/SCT is safe and effective in patients with AL amyloidosis and cardiac involvement.