Hemocompatibility remains a challenge for injectable and/or implantable medical devices, and thromboresistant coatings appear to be one of the most attractive methods to down-regulate the unwanted enzymatic reactions that promote the formation of blood clots. Among all polymeric materials, polyurethanes (PUs) are a class of biomaterials with excellent biocompatibility and bioinertness that are suitable for the use of thromboresistant coatings. In this work, we investigated the thermal and physico-mechanical behaviors of ester-based and ether-based PU films for potential uses in thromboresistant coatings. Our results show that poly(ester urethane) and poly(ether urethane) films exhibited characteristic peaks corresponding to their molecular configurations. Thermal characterizations suggest a two-step decomposition process for the poly(ether urethane) films. Physico-mechanical characterizations show that the surfaces of the PU films were hydrophobic with minimal weight changes in physiological conditions over 14 days. All PU films exhibited high tensile strength and large elongation to failure, attributed to their semi-crystalline structure. Finally, the in vitro clotting assays confirmed their thromboresistance with approximately 1000-fold increase in contact time with human blood plasma as compared to the glass control. Our work correlates the structure-property relationships of PU films with their excellent thromboresistant ability.