Hyperglycemia during cardiopulmonary bypass (CPB) with glucose containing cardioplegia is common; normoglycemia is difficult to maintain and failure to do so may result in worse outcomes. The purpose of this quality improvement initiative was to show that a simple timely insulin bolus is more effective for glucose control during CPB with glucose containing cardioplegia than conventional (not standardized) glucose management in historical case-matched controls. A single bolus of insulin (.2 international units per kilogram; iu/kg) was administered, at the time of aortic cannulation, to 211 consecutive patients undergoing cardiac surgery with CPB and glucose containing cardioplegia. A further .1 iu/kg bolus of insulin was given for blood glucose (BG) measurements greater than 10.0 mmol/L (180 mg/dL) during CPB. The control group of 211 historical case-matched patients had glucose management according to anesthesiologist preference (insulin as a bolus, bolus plus infusion, infusion only, or no insulin). The frequency of hyperglycemia (BG > 11.0 mmol/L; 198 mg/dL) during CPB was significantly less in the study group (22; 10.5%) than in the control group (117; 55.5%) (p < .0001). Hyperglycemia in the first 6 hours in the intensive care unit was also significantly less frequent in the study group (5; 2.4%) than in the control group (14; 6.6%) (p = .03). Severe hypoglycemia (BG < 2.8 mmol/L; 50.4 mg/dL) occurred in one patient (.47%) in the timely bolus insulin group and five patients (2.3%) in the control group (p = .09). The timely bolus insulin method is more efficacious, but equally safe, in preventing hyperglycemia during CPB with glucose containing cardioplegia, compared with conventional (not standardized) insulin treatment in historical case-matched controls.