Atrial fibrillation is a frequent complication of cardiac surgery and the most common reason for delay in discharge from the hospital after open-heart surgery. This review summarizes the results of studies that have examined the prophylactic value of orally administered sotalol and amiodarone in preventing atrial fibrillation after open-heart surgery. The reduction in the prevalence of postoperative atrial fibrillation is 50-90% for sotalol compared with 50-60% for amiodarone. Sotalol has a rapid onset of action, allowing it to be efficacious when used orally shortly after surgery. In contrast, amiodarone has a slow onset of action that necessitates either oral loading for several days before surgery or intravenous loading shortly before or after surgery. However, although patients who are poor candidates for beta blockade may not tolerate sotalol, amiodarone does not have this limitation. Although both sotalol and amiodarone have relative advantages and disadvantages, available data indicate that either agent can be used effectively in selected patients to reduce the risk of postoperative atrial fibrillation. Larger controlled comparative trials are needed to define the precise magnitude of benefit from these compounds relative to their side effect profiles.