Postoperative atrial fibrillation is a common complication after open heart surgery; it increases morbidity, hospital stay, and costs. In an analysis of 8 large cardiac surgery trials totaling 20,193 patients, the incidence of postoperative atrial fibrillation was estimated to be 26% and ranged from 17% to 35%. We reviewed the results of 52 studies published between 1966 and 2003 that evaluated pharmacologic strategies to prevent postoperative atrial fibrillation in nearly 10,000 patients undergoing open heart operations. Supraventricular tachyarrhythmias, including atrial fibrillation, after open heart operations occurred in 29% of patients who did not receive prophylactic drugs, compared with 12% in patients who received intravenous followed by oral amiodarone, 15% in those given sotalol, 16% in those given oral amiodarone, and 19% in those given beta-blockers. Pharmacologic strategies and regimens aimed at preventing postoperative atrial fibrillation are necessary to optimize the postoperative care of patients undergoing open heart operations. Although no strategy has consistently been shown to be superior to another, the most effective approach to preventing postoperative atrial fibrillation likely involves multiple interventions. In the absence of contraindications, all patients should receive beta-blocker therapy before and after the operation. For patients with 1 or more risk factors for postoperative atrial fibrillation, regimens consisting of either sotalol (beta-blocker with class III antiarrhythmic properties) alone or beta-blockers in combination with amiodarone seem to be the safest, most effective pharmacologic strategies for preventing postoperative atrial fibrillation.