A randomized, placebo-controlled study examined the effect of amiodarone on the incidence of ventricular arrhythmias after acute myocardial infarction (AMI). Two hundred patients with AMI were randomized to receive amiodarone, 200 mg every 8 hours for 1 month, followed by 200 mg/day, or placebo, starting 48 hours after the onset of chest pain. Twenty-four-hour Holter monitoring was performed on day 1, repeated after 8 days and subsequently at 3-month intervals. One hundred seventy-two patients were followed for 6 to 42 months and monitor data were available at 6 to 9 months in 129 patients. Amiodarone was well tolerated, with no serious side effects; 12 patients were withdrawn from therapy. At 6 to 9 months more than 1 ventricular premature complex per hour was present in 3 of the 59 amiodarone-treated patients (5%) and 24 of the 70 placebo-treated patients (34%) (p less than 0.02). Complex arrhythmias (multifocal, early cycle, repetitive, bigeminy, trigeminy or ventricular tachycardia) were present in 5 of 59 of the amiodarone-treated patients (8%) and 20 of 70 placebo-treated patients (28%) (p less than 0.005). Sixteen patients in the amiodarone group and 11 in the placebo group died (difference not significant). Thus, amiodarone can reduce the frequency and complexity of ventricular arrhythmias after AMI, but it is unlikely that this will result in a substantial beneficial effect on post-AMI mortality risk.