139 patients undergoing cardiac surgery were included in a prospective, randomized trial. Patients were randomly allocated to receive cardiopulmonary bypass (CPB) with Trillium Biopassive Surface (TBS Group) coated oxygenators or conventional circuits (control group). 112 patients were studied with respect to postoperative biochemical profile; a subgroup of 27 patients was studied with respect to perioperative complement (C3a) activation. Patients in the TBS group demonstrated a significantly lower white blood cell count at the end of the operation (p=0.036) and a significantly higher platelet count the day after the operation (p=0.023) when compared to the control group. C3a was significantly higher (p=0.02) in the TBS group after 30 minutes of CPB, but the C3a increase after protamine administration was significantly less pronounced in the TBS group vs. the control group. Further studies involving platelet and leukocyte activation are required to better elucidate the action of this new coating in the setting of routine CPB.