The marked tendency to promote thrombogenesis is a major obstacle for the implementation at the clinical level, of regenerative vascular grafts derived from extracellular matrices such as the small intestinal submucosa (SIS). SIS has around 66% (w/w) content of the extremely thrombogenic type I Collagen, which is appropriate for regeneration purposes, but still problematic for cardiovascular applications. To overcome this major hurdle, we covalently conjugated addition-fragmentation chain-transfer (RAFT) polymerized macromolecules of Zwitterionic Phosphorylcholine (PC) on dried SIS tubes previously formed from decellularized wet sheets. Our results indicate that even after a low covalent conjugation yield via 1-Ethyl-3-(3dimethylaminopropyl) carbodiimide (EDC), platelet deposition decreased by about 94% with respect to the unmodified surface. This was also the case when compared with the commercially available vascular graft material expanded polytetrafluoroethylene (ePTFE), where platelet deposition decreased by nearly 93% Thermal stability of modified SIS as well as regenerative and proliferation abilities remained unchanged as evidenced by constant melting temperatures and high growth levels of HUVEC cells after 3 and 8 days. Low cytotoxic levels were detected, and mechanical properties were improved, resembling the mechanical behavior of the native carotid artery. The combination of attributes of the modified material make it attractive for the next generation of regenerative vascular grafts.