Segmented polyurethane (SPU) materials based on different soft-segment component (PPG, PTMO and PBA) and various length of soft-segment (molecular weight of PBA: 500, 700 and 1000) were synthesized in this research. The soft-segment components were synthesized from polyether-polyols (PPG and PTMO) or from polyester-polyol (PBA). The physical properties and structure characterization of the synthesized SPUs were fully investigated using differential scanning calorimetry (DSC) analysis, and stress-strain measurements. Blood compatibility was evaluated with the platelet adhesion ratio (PAR) and the morphological observation for adhering platelets. Our results showed that the physical properties and blood compatibility of SPUs were closely related to its composition, which was controlled by (1) the types of the soft-segment component employed and (2) the length of soft segments. Polyether-polyol-based SPUs exhibited greater phase separations, poorer tensile strengths, and better blood compatibility, compared with polyester-polyol-based SPUs. SPUs with shorter soft-segment component exhibited greater phase mixing, higher tensile strength, but lower blood compatibility of SPUs, as compared with its counterparts with longer soft-segment component.