Extracorporeal circulation (ECC) catheters have potential to be blood compatible and could be used to prevent thrombotic occlusion. Here, we produced heparin-mimicking anticoagulation PVC tubing on a large scale by synthesizing a heparin-mimicking polymer (HMP) and co-extruding. The PVC@HMP catheter was evaluated using whole human blood in vitro, which indicated it could prevent plasma protein attachment, reduce platelet adhesion and activation, and inhibit coagulation factors (XII, XI, IX, and VIII). Moreover, the anticoagulation PVC tubing was assembled into extracorporeal circulation with a New Zealand rabbit model, manifesting excellent real-time antithrombogenic properties without systemic heparin anticoagulation in vivo. The rapid recovery of coagulation factors after operation further confirmed its superiority over heparin, which would not completely inactivate the activity of those coagulation factors (XII, XI, IX and VIII). In addition, the PVC@HMP-1 catheters remain patent after being implanted in rats for 28 days without apparent inflammation and mortality complications. The anticoagulation PVC tubes could be used to construct various systemic and integrative anticlotting biomedical devices, which would dramatically reduce the introduction of heparin into blood circulation, thus preventing side effects and promoting the development of heparin-free treatment.