Isolated aortic valve replacement (AVR) or coronary artery bypass grafting (CABG) using minimized extracorporeal circulation (MECC) has been shown to have less deleterious effects than standard cardiopulmonary bypass (CPB). In this prospective cohort study, we evaluated and compared clinical results of combined AVR with CABG using MECC. We prospectively collected preoperative, intraoperative, postoperative and follow-up data of 65 patients who underwent combined AVR with CABG using MECC and compared these with 135 patients undergoing combined AVR with CABG using standard CPB. No significant differences were seen in patients demographic characteristics or intraoperative data. Patients in the MECC group experienced a smaller preoperative haemoglobin drop (4.5±0.8 g/dl vs. 5.0±0.5 g/dl, P=0.002) resulting in higher haemoglobin at discharge (11.3±1.3 g/dl vs. 10.8±1.1 g/dl, P=0.03). They had decreased blood products requirements (P=0.004) compared to patients in the standard CPB group. No differences were noted in pulmonary complications, neurological events or mortality. We present for the first time data showing that combined AVR with CABG using MECC is feasible and provides better clinical results compared to standard CPB with regard to blood products requirements, without compromising operative morbidity or mortality.