Background. Postoperative atrial fibrillation after cardiac operation is common. Despite the identification of risk factors associated with postoperative atrial fibrillation, the pathophysiologic mechanisms remain unclear. Myolysis has been recently described to be associated with maintenance of atrial fibrillation in experimental animals. In this study, we attempted to identify histopathologic changes in atria that might predict the development of postoperative atrial fibrillation, and Specifically address its association with myolysis. Methods. Right appendicular atrial tissue was sampled before and after cardiopulmonary bypass from 60 patients in sinus rhythm who underwent elective coronary artery bypass grafting. Results. Fifteen patients (25%) developed postoperative atrial fibrillation. Histopathologic abnormalities were found in most patients (52 of 60). However, only myolysis and lipofuscin levels were found to be an independent histologic finding associated with the development of postoperative atrial fibrillation. Electron microscopy showed that myolytic vacuoles were not membrane bound, and were associated with lipofuscin deposits. Neither mitochondrial pathology nor apoptosis was detected in the atria before or after operation. Conclusions. Abnormalities in biopsies before cardio-pulmonary bypass can indicate the susceptibility to develop postoperative atrial fibrillation. This implies that the status of the atrium before cardiopulmonary bypass is a major determinant in the development of this common complication.