Background: Postoperative AF leads to significant morbidity and prolongation of hospital stay, and complicates 20% to 40% of surgical procedures requiring cardiopulmonary bypass (CPB).(1) This study aims at measuring The efficacy of Plasminogen Activator Inhibitor-1 (PAI-1) as a predictor of postoperative atrial fibrillation after Cardiopulmonary Bypass (CPB). Methods and Results: We enrolled 100 adult patients undergoing elective cardiac surgery requiring CPB and who were in sinus rhythm at the time of surgery. Blood samples were obtained for measurement of plasminogen activator inhibitor-1 (PAI-1) in the morning of the operation and immediately after separation from CPB and administration of protamine. Patients who developed postoperative AF (28 patients, 28%) were significantly older (P=0.04), had history of hypertension (P=0.035) , performed graft to right coronary artery (P<0.001), performed greater number of grafts (P=0.014), subjected to longer time of cardiopulmonary bypass (CPB) (P=0.032), subjected to postoperative administration of epinephrine and dobutamine (P=0.005), had lower postoperative ejection fraction (P=0.028), had postoperative myocardial ischemia (P<0.001), had higher serum level of preoperative PAI-1 (P=0.0005), higher serum level of postoperative PAI-1 (P<0.0001), had larger left atrial diameter > 4 cm (P<0.0001), had longer length of ICU stay (P=0.04), and needed postoperative mechanical ventilation (P=0.0026) receiver-operating characteristic (ROC) curve for prediction of postoperative atrial fibrillation using preoperative PAI-1 level. The best cut-off value was a preoperative PAI-1 level of >15ng/ml, and the receiver-operating characteristic (ROC) curve for prediction of postoperative atrial fibrillation using post-CPB PAI-1 level. The best cut-off value was a post-CPB PAI-1 level of > 23ng/ml. Conclusion: An elevated preoperative or postoperative PAI-1 antigen concentration is an independent predictor for development of AF after CPB. Studies are needed to determine whether drugs that reduce PAI-1 concentrations can also reduce the risk of postoperative AF.