Coating strategies play a pivotal role in anticoagulation management during extracorporeal circulation. While heparin-based coatings remain the most widely used, their limited anticoagulant efficacy may lead to adverse events such as postoperative bleeding, hypokalemia and heparin-induced thrombocytopenia (HIT). The development of novel anticoagulant coatings is therefore crucial to overcome these limitations and improve therapeutic outcomes. Herein, we developed a nanoconjugated anticoagulant coating with excellent blood-repellency, thereby prolonging clotting time and reducing the complications commonly linked to drug-eluting coatings. Evaluation via coagulation time assays demonstrated that the nanoconjugated anticoagulant coating extends clotting time by 73% compared to a commercial heparin-based coating. Biocompatibility was confirmed through both in vitro and in vivo cytotoxicity tests. After 3 h of blood immersion, the silicon mass fraction remained as low as 0.01%, indicating excellent coating stability. These findings underscore the promising clinical potential of blood-repellent interfaces in medical devices for extracorporeal circulation.