Objective: To assess the effect of preoperative amiodarone treatment on patient mortality after heart transplantation. Design: Retrospective study. Setting: Single-institution university hospital. Participants: One hundred six consecutive patients with heart transplants. Interventions: None. Measurements and Main Results: Patients were grouped according to duration of preoperative amiodarone treatment, and posttransplant mortality before hospital discharge was compared with patients not treated with amiodarone. The authors collected cardiovascular data in the preoperative and postoperative periods. There was a significant increase in posttransplant mortality before hospital discharge in patients treated with amiodarone for more than 4 weeks in the preoperative period ( p < 0.05). Patients treated with amiodarone had significantly lower ( p < 0.05) heart rates (mean heart rate, 103 ± 19 beats/min) in the early postoperative period than patients not treated with amiodarone (mean heart rate, 111 ± 15 beats/min), but there was no relationship with mortality ( p = not significant). Patients who died had a significantly lower ( p < 0.05) postoperative cardiac index (2.2 ± 0.7 to 2.5 ± 0.7) in the first 24 hours after cardiopulmonary bypass compared with patients who survived to hospital discharge (3.0 ± 0.7 to 3.1 ± 0.9), but there was no relationship to amiodarone treatment ( p = not significant). Conclusion: Preoperative amiodarone treatment for more than 4 weeks may be associated with a significant increase in postoperative mortality in patients undergoing heart transplantation. Therefore, the indications for amiodarone must be carefully considered and, if needed, the maintenance dose should be kept to a minimum.