To develop better blood compatible polymer for long-term biomedical applications, poly(ethylene oxide) (PEO) grafted and/or heparin immobilized polyurethanes (PUs) were made by novel surface modification. Their blood compatibilities were investigated using in vitro platelet adhesion test, APTT, PT, immobilized heparin bioactivity measurement, and ex vivo rabbit A-A shunt test. In platelet adhesion tests, PEO grafted PU surfaces, compared to PU control, displayed very little platelet adhesion and activation, and this effect was more significant as the molecular weight of PEO increased from 200 to 2000. Also, the degree of platelet adhesion was lower in the heparinized PU surfaces than that of PU control. The immobilized heparin showed a greater effect on intrinsic blood coagulation factors than on extrinsic ones, whereas the PU-PEO surface was independent of blood coagulation factors. Lowering both in vitro platelet adhesion and activation led to a prolongation in the ex vivo occlusion time. In particular, the heparinized PU-PEO surfaces displayed enhanced blood compatibility due to the synergistic effects of PEO and heparin.