Amiodarone has been proposed to decrease atrial fibrillation after cardiac surgery. The literature was systematically reviewed for randomized trials comparing amiodarone with control for prevention of atrial fibrillation. Data were extracted on study characteristics, quality, and incidence of atrial fibrillation, cardiovascular outcomes, and length of hospitalization. Nineteen trials were included. Amiodarone reduced the odds ratio of atrial fibrillation (0.50; 95% confidence interval [CI]: 0.43 to 0.59, p < 0.0001), ventricular tachyarrhythmias (0.39; 95% CI: 0.26 to 0.58, p < 0.0001), and strokes (0.53; 95% CI: 0.30 to 0.92, p = 0.02). Amiodarone reduced hospital stay (0.6 days; 95% CI: 0.4 to 0.8, p < 0.0001). Amiodarone decreased atrial fibrillation, reduced perioperative ventricular tachyarrhythmias and strokes, and reduced duration of hospitalization. The current evidence supports recommending the routine use of perioperative amiodarone for cardiac surgery.