We examined the influence of preoperative therapy with amiodarone on the incidence of acute organ dysfunction after cardiac surgery in a matched case-control study. There were 220 case-control pairs matched by day of surgery, source of admission, demographic characteristics, placement of intraaortic balloon pump before surgery, repeat operations, emergency surgery, thoracic aorta surgery and other surgical procedures. History of congestive heart failure was more prevalent in the amiodarone group than in the control group before surgery (60% vs 38%, P < 0.0001). The incidence of acute organ dysfunction, duration of mechanical ventilation, and death was similar in both groups after surgery. The requirement for inotropes (26% vs 17%, P = 0.03) and vasopressors (66% vs 55%, P = 0.02) and the incidence of postoperative nosocomial infections (12% vs 6%, P = 0.04) was greater in the amiodarone group. However, the difference was not significant after adjustment for congestive heart failure (Cochran-Mantel-Haenszel test P = 0.15, P = 0.25, P = 0.16, respectively). Amiodarone did not increase the incidence of acute organ dysfunction or death after cardiac surgery. The requirement for inotropes and vasopressors and the incidence of nosocomial infections were related to the severity of the underlying cardiac disease. The practice of discontinuing amiodarone treatment before surgery to reduce the incidence of postoperative organ dysfunction should be critically reevaluated. Implications: Amiodarone is often used for the treatment of life-threatening rhythm disorder. Amiodarone has been blamed for causing organ injury after cardiac surgery. In a study of 220 patients, amiodarone did not increase the risk of organ injury or death after cardiac surgery when compared with control patients. There was no evidence to support the practice of stopping amiodarone before cardiac surgery to avoid serious complications.