A recent randomized trial of higher versus lower mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) showed that higher MAP on CPB was associated with a lower incidence of overall cardiac and neurologic morbidity and mortality in coronary artery bypass graft surgery (CABG) patients. Cardiopulmonary bypass MAP was controlled pharmacologically while CPB flow was held constant for any given period. The objective of the present study was to assess the efficacy and safety of this pharmacologic protocol. Two hundred forty-eight patients participated in the study; the mean age was 65.8 ± 9.4 years, 20% were women, and the mean preoperative ejection fraction was 48%. The low-flow corrected CPB MAP attained for the low and high MAP groups was 56.7 ± 5.0 mmHg and 77.7 ± 7.1 mmHg, respectively (p = 0.0001). Major cardiac and neurologic outcomes, postoperative blood loss, renal dysfunction, intensive care unit (ICU) stay, and duration of intubation were not found to be significantly associated with any drug in the pharmacologic protocol. These findings support that the pharmacologic protocol used to maintain CABG patients at higher MAP on CPB is both efficacious and safe.