Background: We aimed to evaluate if the use of an intra-aortic balloon pump (IABP) during cardioplegic arrest improves organ function and reduces endothelial activation in patients undergoing coronary artery bypass graft (CABG). Methods and Results: Five-hundred and one CABG patients were randomized into 2 groups: (Group A n=270) linear cardiopulmonary bypass (CPB); and (Group B n=231) automatic 80beats/min IABP-induced pulsatile CPB. We evaluated hemodynamic response, coagulation and fibrinolysis, transaminase, bilirubin, amylase, lactate, renal function (estimated glomerular filtration rate [eGFR], creatinine and any possibility of renal insufficiency or failure), respiratory function and endothelial markers (vascular endothelial growth factor [VEGF] and monocyte chemotactic protein-1 [MCP-1]). IABP, which induced surplus hemodynamic energy, was 21,387±4,262ergs/cm³. Group B showed lower chest drainage, transfusions, international normalized ratio, and antithrombin III, together with higher platelets, activated partial thromboplastin time, fibrinogen and D-dimer. Transaminases, bilirubin, amylase, lactate were lower in Group B; there were better results for eGFR in Group B from ICU-arrival to 48h, resulting in lower creatinine from ICU-arrival to 48h. The necessity for renal replacement therapy was lower in Group B Stage-3. Group B P_aO₂/F_iO₂ and lung compliance improved with aortic de-clamping on the first day with shorter intubation time. Group B showed lower VEGF and MCP-1. Conclusions: Pulsatile flow by IABP improves whole-body perfusion and reduces endothelial activation during CPB. (Circ J 2012; 76: 1121-1129)