Background-Atrial fibrillation (AF) is a frequently encountered arrhythmia after cardiac surgery, but its underlying mechanisms are still unclear. We hypothesize that autoimmune and inflammatory responses against heat shock protein 65 (HSP65) may be involved and hence examined the relationship between HSP65 autoantibodies and occurrence of postoperative AF. Methods and Results-A prospective study of 329 patients undergoing elective primary CABG was undertaken.Cardiovascular risk factors, ECG characteristics, medications, and intraoperative and postoperative features were documented. Anti-HSP65 antibodies and C-reactive protein levels were measured in all preoperative blood samples with ELISA. Postoperative AF was defined as the characteristic arrhythmia, lasting for at least 15 minutes and confirmed on 12-lead ECG and occurring within the first postoperative week. This occurred in 62 patients (19%). In univariate analysis, HSP65 antibodies were significantly higher in patients with postoperative AF (Pϭ0.02). History of previous myocardial infarction, duration of bypass, number of distal anastomosis, and duration of ventilation were also associated with AF (PϽ0.05), but C-reactive protein levels were not (Pϭ0.