Miniaturized cardiopulmonary bypass (CPB) systems, though more biocompatible, are limited by not being adaptable to all cardiac surgical operations. We evaluate a versatile CPB system [extracorporeal vacuum-assisted device optimized (EVADO)] based on the elimination of roller pumps, separation of extracavitary suctioned blood and state-of-the-art technology for oxygenator systems and digital control. We randomized 165 patients to either EVADO or conventional CPB (cCPB). Surgery could be completed in all cases without conversion to cCPB. The use of EVADO significantly reduced the intraoperative haemolysis (lesser increase in free hemoglobin, P<0.001 vs. control, and lesser decrease in haptoglobin levels, P=0.001 vs. control). Among patients who were submitted to EVADO, postoperative bleeding (P=0.004), transfusions (P=0.046), rate of revision for bleeding (P=0.03), rate of postoperative atrial fibrillation (P=0.007), time to extubation (P=0.02) and ICU stay (P=0.04) were reduced. The clinical benefits associated with the EVADO may be due to better end-organ perfusion, lesser impairment of the coagulation and inflammatory reaction.