Application of heparin bonded surfaces (HBS) in the extracorporeal circuit (ECC) might avoid or at least reduce conventional heparin administration and would be of great benefit, especially in long-term perfusion. In this study, six sheep had a veno-venous bypass using membrane oxygenators with either total HBS or, in a control group, with untreated surfaces. Under strictly standardized conditions (body weight, drugs, geometry of tube, catheters, etc.), the animals in both groups received 300 IU/kg heparin before the catheterization as a bolus injection. In both groups, the measured heparin level decreased within 6 hours to zero, accompanied by a fall of other coagulation parameters (ACT, PTT etc.) to normal. In the control group, the ECC failed at this point because of clots in the oxygenators, whereas perfusions using HBS continued without further changes in clotting parameters until 12, 22, and 53 hours when the experiments were stopped intentionally. During the first 6 hours platelets showed a similar decrease in number in both groups and were comparable with conventional heparin treatment during further ECC periods. Other parameters, such as AT III, FXa, fibrinogen, and leukocytes were normal in both groups. The plasma hemoglobin increased markedly at the end of perfusion time in the control group but remained low even after 53 hours of ECC with HBS. The results indicate that the use of such completely heparin bonded systems can lead to a drastic reduction in systemic heparin administration.