Endothelialization is an ideal approach to improve the blood compatibility of synthetic polymers. However, cell detachment is inevitable under shear flow conditions. Therefore, the issue of blood compatibility needs to be addressed for both the bare and the endothelialized polymer. RGD-containing polymer P-GS5 was synthesized by modification of poly(D,L-lactide-co-beta-malic acid) (PLMA) with the peptide GRGDS. The compositions, molecular weights and hydrophilicities of poly(D,L-lactide) (PDLLA), PLMA, and P-GS5 were characterized by nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopy (XPS), gel-permeation chromatography (GPC) and water contact angle measurements, respectively. The blood compatibilities of the bare and the endothelialized polymers were evaluated by clotting time and platelet adhesion tests. The results showed that the coagulation pathways were not influenced before and after cell culture; the bare P-GS5 attracted less platelet adhesion and induced lower pseudopodia extension compared with PDLLA and PLMA, and the platelet adhesion on P-GS5 was almost completely eliminated after cell seeding. The results suggest that P-GS5 could be a potentially useful material in vascular tissue engineering.