Statin therapy in nonsurgical patient populations is associated with a significant reduction in adverse cardiovascular events, including death, myocardial infarction (MI), and stroke. Recently, statin therapy was shown to be associated with a reduced incidence of postoperative mortality in patients undergoing major noncardiac vascular surgery. We investigated the influence of preoperative statin therapy on adverse outcomes after primary coronary artery bypass graft (CABG) surgery. A retrospective cohort study of patients undergoing primary CABG surgery with cardiopulmonary bypass (CPB) (n=1663) between January 1, 2000 and December 31, 2001 at the Texas Heart Institute was performed. Patients were classified into 2 groups: patients receiving preoperative statin therapy (n=943) and patients not receiving preoperative antihyperlipidemic therapy (n=720). To determine if preoperative statin therapy was independently associated with a reduction in the risk of adverse postoperative outcomes, multivariate stepwise logistic regression was performed controlling for patient demographics, medical history, and preoperative medications. Multivariate logistic regression analysis demonstrated that preoperative statin therapy was independently associated with a significant reduction ( approximately 50%) in the risk of 30-day all-cause mortality (3.75% versus 1.80%; P<0.05). The adjusted odds ratio for early mortality in patients receiving preoperative statin therapy compared with patients not receiving antihyperlipidemic agents was 0.53 (95% CI, 0.28 to 0.99). Statin therapy was not independently associated with a reduced risk of postoperative MI, cardiac arrhythmias, stroke, or renal dysfunction. In an attempt to further control for selection bias related to the choice of therapy, multivariate analysis of a propensity-matched cohort of 1362 patients revealed that preoperative statin therapy was independently associated with a significant reduction in the composite endpoint of 30-day all-cause mortality and stroke (7.1% versus 4.6%; P<0.05). Preoperative statin therapy may reduce the risk of early mortality after primary CABG surgery with CPB.