Background: Although guidelines recommend the use of beta-adrenoceptor blocking drugs to reduce cardiac events (CEs) after major noncardiac surgery, trial results have varied between showing benefit, ineffectiveness, and harm. We sought whether optimizing beta-blockade (BB) delivery could make them more effective. Methods: Intermediate risk patients undergoing major noncardiac surgery (n = 400) were randomized to 2 strategies of BB therapy: universal BB (UBB; n = 197) comprising an algorithm-based, nurse-led strategy to optimize dosing and adherence to bisoprolol titration over ≥1 week preoperatively versus usual care (UC; n = 203), whereby BB are continued in those already taking them or prescribed for patients identified as high risk based on ischemia (new or inducible wall motion abnormalities) at dobutamine echocardiography (DbE). Daily electrocardiogram and troponin levels were obtained on 3 postoperative days. The primary end point was a major CE (cardiac death or myocardial infarction) within 30 days. Results: There were 25 major CEs (6.3%), occurring in 13 (6.6%) of 197 UBB and 12 (5.9%) of 203 UC patients (OR 1.12, 95% CI 0.52-2.39). Independent predictors of CEs were baseline systolic blood pressure (β 1.02, P = .005) and postoperative hypotension (β 1.02, P = .03) but not treatment strategy. Those randomized to UBB had significantly better heart rate control perioperatively, at the cost of bradycardia and hypotension. The negative predictive value of DbE in this study was 95%. Conclusions: These data confirm a persistent CE rate after major noncardiac surgery despite nurse-led dose titration of bisoprolol. Cardiac events were equivalent to a UC strategy based on DbE results.