Background: Atrial fibrillation (AF) after cardiac surgery is associated with significant morbidity. We investigated whether preoperative statin therapy was associated with decreased incidence of postoperative AF in patients undergoing cardiac surgery, including isolated valve surgery and patients with low ejection fraction (EF). Methods: A retrospective study of consecutive patients without history of AF (n = 4044) who underwent cardiac surgeries at St. Luke's Episcopal Hospital (Houston, TX), from January 1, 2003, through April 30, 2006, was conducted. Postoperative AF was assessed by continuous telemetry monitoring during hospitalization for cardiac surgery. Results: A total of 2096 patients (52%) received preoperative statins. Atrial fibrillation occurred in 1270 patients (31.4% in both the statin and nonstatin groups). In multivariate regression analysis, age >65 years, history of valvular heart disease, rheumatic disease, pulmonary disease, and New York Heart Association class III/IV were independent predictors of increased risk, whereas female sex was associated with decreased risk. Preoperative statin therapy was not associated with decreased risk in the entire cohort (odds ratio [OR] 1.13, 95% confidence interval [CI] 0.98-1.31) or in subgroups undergoing isolated coronary artery bypass grafting (OR 1.16, 95% CI 0.97-1.43), isolated valve surgery (OR 1.09, 95% CI 0.81-1.46), or both (OR 1.09, 95% CI 0.72-1.65), or the subgroup with EF <35% (OR 1.23, 95% CI 0.84-1.82). After propensity score analysis (n = 867 patients in each group), preoperative statin therapy was not associated with decreased AF incidence (OR 1.14, 95% CI 0.92-1.41). Conclusions: Preoperative statin therapy was not associated with decreased incidence of postoperative AF in patients undergoing cardiac surgery, including patients with low EF.