The aim of the study was to evaluate the effects of phosphorylcholine coating (PC) on intra-operative extracorporeal circulation (ECC) management and perioperative outcome. One hundred and twenty consecutive cardiac surgery patients were enrolled for the study. Patients were randomly assigned to ECC with PC circuits (60 patients) or to corresponding non-coated circuits (60 patients). Trans-oxygenator pressure drop, blood flows, flow resistances and ECC parameters were recorded at surgery before ECC institution and every 10 min thereafter until ECC discontinuation. Postoperative variables (hematological parameters, drainage blood loss, mechanical ventilation time, incidence of atrial fibrillation, use of blood products) were also assessed and compared between groups. No differences were found between the two groups in terms of demographics, operative, and hematological profiles. PC showed, at equal pump flows, to significantly (P<0.01) attenuate pressure drop across oxygenators and to reduce oxygenator inlet pressures during ECC. Postoperatively, PC showed to remarkably reduce platelet consumption. Coating showed also to reduce postoperative blood loss, although the difference did not reach statistical significance. No differences between the two groups were found in terms of additional perioperative effects. The use of PC in low-risk elective cardiac surgery patients enhances ECC management, by means of a less restrictive trans-oxygenator blood flow.