Postoperative atrial arrhythmias after cardiac surgical procedures are common, with a reported overall incidence of approximately 50%. The pathophysiological mechanisms responsible for atrial fibrillation after a cardiac procedure remain unclear, although several clinical studies published during the past decade have identified certain preoperative risk factors associated with postoperative atrial fibrillation. In this study, we attempted to identify the histopathological changes in atrial cardiomyocytes that might predict the development of atrial fibrillation during the postoperative period. Atrial tissue from 60 patients was sampled before and after a cardiopulmonary bypass. Fifteen patients (25%) developed postoperative atrial fibrillation. The only clinical independent risk factor for the development of postoperative atrial fibrillation was chronic obstructive pulmonary disease (COPD) (P = .037). Histologically, there were 3 findings in the atrial myocardium that were more common in patients who developed postoperative atrial fibrillation: (1) vacuolation size (P = .017), (2) vacuolation frequency (P = .0136), and (3) lipofuscin content (P = .013). The identification of these histological markers for the development of postoperative atrial fibrillation may contribute not only to our understanding of the underlying pathophysiology that leads to postoperative atrial fibrillation but also to a method of preventing this troublesome complication of cardiac surgery.