The aim of this study is to investigate how the presence of liquid crystal, cholesteryl oleyl carbonate, embedded into polymers (PMMA, Eb270, PU) affects the biocompatibility of composite membranes with human blood. The effects of different surface textures of composite membranes on platelet adhesion and platelet activation were evaluated as well. The adhesion and geometric deformation of platelets were demonstrated by SEM. The quantitative assay of platelet activation was determined by measuring the production of P-Selectin, and by measurement of the blood clotting index when PRP blood was incubated with pure polymer films and composite membranes. Moreover, the hemolysis studies on the damage to red blood cells were performed to gain information on the hemocompatibility of these biomaterials. The results showed that inclusion of cholesteryl oleyl carbonate (COC) embedded in composite membranes, improves their biocompatibility with respect to a substantial reduction of platelet adhesion and the controlled decrease of platelet activation. As the COC content of composite membranes was increased, the value of the blood clotting index increased and the production of P-Selectin decreased. The results also showed that the presence of COC resulted in a decrease of hemolysis ratios. Comparing among three different composite membranes, the best biocompatibility is achieved when PU/COC> or ==Eb270/COC>PMMA/COC. The in vitro studies performed in this work suggest that it may be reasonable to use liquid crystal COC as a mean of surface modification to improve the blood compatibility of biopolymers.