Objectives: Bioactive Carmeda™ heparin-coated extracorporeal circuits (ECC) reduce the contact phase and coagulation activation during cardiopulmonary bypass (CPB). Thus, heparin-coating allows safe reduction of anticoagulation during routine CPB. A new biopassive coating, the Balance™ Biosurface, containing negatively charged sulphonated polymers, recently became available. This study aimed to compare clotting activation and thrombo-resistance of the Balance™ (B) with the Carmeda™ (C) circuit under full (FDH) and low (LDH) doses of systemic heparin. Methods: Forty experiments were performed using an ex vivo study set-up consisting of a simplified ECC and circulation of fresh human donated blood. LDH or FDH were obtained using 0.5 IU/ml or 1 IU/ml heparin to reach target activated clotting time (ACT) at 250 s or 500 s respectively. Four groups were designed, FDH-C, FDH-B, LDH-C and LDH-B (all groups n = 10). Blood sampling took place before and during two hours of CPB. Coagulation activation was assessed (FXIIa, F1.2) as well as scanning electron microscope imaging of oxygenators with determination of adhesion scores. Results: Regardless of LDH or FDH regimen, the mean ACT was lower using the biopassive compared to the bioactive surface (P < 0.001), whilst total dose of heparin to maintain ACT over the target level was higher (P < 0.001). However, FXIIa and F1.2 were similar between groups throughout the experiments, as well as pressure gradients among oxygenators. Adhesion scores after ultrastructural assessment of oxygenators were similar between groups. Conclusions: Without surgically related haemostatic disturbances and based on target ACT levels under low or full dose heparin, the clotting process was similar between the heparin-coated and the new sulphonated polymer-coated ECC, which showed similar thrombo-resistance.