The use of perioperative beta-blockers has been debated for decades. Now, a large study from the U.S. Department of Veterans Affairs (VA) suggests that the drugs may be of benefit in selected patients. In a retrospective cohort analysis, exposure to beta-blockers on the day of or the day following noncardiac surgery was evaluated among a population-based sample of nearly 137,000 patients from 104 VA medical centers. The main outcome was all-cause 30-day mortality and cardiac morbidity. Overall, 55,138 patients (40%) were exposed to beta-blockers, although the rate was nearly 68% in those undergoing vascular surgery. Exposure increased with increased cardiac risk factors. Death occurred in just over 1% of patients and cardiac morbidity occurred in just under 1%. Overall, exposure to beta-blockers was associated with a lower mortality (relative risk [RR] 0.73%; 95% confidence interval [CI], 0.65-0.83; P < 0.001; number needed to treat [NNT], 241). The effect was greater in patients with higher cardiac risk factors, which include high-risk surgery, cerebrovascular disease, ischemic heart disease, heart failure, diabetes, and renal insufficiency. When stratified by the revised Cardiac Risk Index variables, patients with two or more cardiac risk factors had a RR of 0.63 (95% CI, 0.50-0.80; P < 0.001; NNT, 105), with three risk factors the RR was 0.54 (95% CI, 0.39-0.73; P < 0.001; NNT, 41), and with four or more risk factors the RR was 0.40 (95%CI, 0.25-0.73; P < 0.001; NNT, 18). This effect was limited to patients undergoing nonvascular surgery. Beta-blocker exposure also significantly reduced the rate of nonfatal Q-wave infarction or cardiac arrest by 37%. The authors conclude that in patients undergoing noncardiac, nonvascular surgery, perioperative beta-blockers significantly reduced 30-day all-cause mortality in patients with two or more cardiac risk factors and support the use of the drugs in these patients. They also suggest a multicenter randomized trial to assess the benefit in patients with low-to-intermediate risk. The authors were unable to find a benefit in stroke risk or in patients undergoing vascular surgery. They were also unable to determine if various beta-blockers (such as metoprolol vs atenolol) were of benefit or if the benefit was from various dosing regimens. (JAMA 2013; 309:1704-1713).