OBJECTIVE: To determine the impact of perioperative beta-adrenergic receptor (betaAR) antagonist administration on neurologic complications. DESIGN: Observational database analysis. SETTING: A clinical investigation at a single tertiary academic medical center. PARTICIPANTS: Elective coronary artery bypass graft surgical patients operated on in the period 1994-1996. INTERVENTIONS: Patients were divided into 2 groups: (1) patients given betaAR antagonist-blocking drugs in the perioperative period, including during operation, and (2) patients not given betaAR antagonists. MEASUREMENTS AND MAIN RESULTS: betaAR antagonist use in 2,575 consecutive patients undergoing coronary artery bypass graft surgery (1994-1996) was determined using the Cardiovascular Database and Anesthesia Information System Database. Outcome variables were postoperative stroke, coma, and transient ischemic attack. Of patients, 113 (4.4%) had postoperative neurologic complications, including stroke (n = 44), coma (n = 12), and transient ischemic attack (n = 3). Of patients, 2,296 (89%) received perioperative betaAR antagonist therapy, and 279 (11%) did not. Adverse neurologic events occurred in 3.9% (n = 90) of patients who received perioperative betaAR antagonists and 8.2% (n = 23) of patients who did not receive betaAR antagonists (odds ratio, 0.45; 95% confidence interval, 0.28 to 0.73; p = 0.003, unadjusted.) Severe neurologic outcomes (stroke and coma) occurred in 1.9% (n = 44) of patients who received betaAR antagonists and 4.3% (n = 12) of patients who did not receive betaAR antagonists (odds ratio, 0.43; 95% confidence interval, 0.23 to 0.83; p = 0.016). CONCLUSION: Use of beta-adrenergic antagonists was associated with a substantial reduction in the incidence of postoperative neurologic complications. A prospective randomized trial is needed to verify this potentially important neuroprotective strategy in cardiac surgery.