The goal of this study was to design a coating that improves the hemocompatibility of blood-contacting polyurethanes (PUs). The proposed modification method involves a two-step reaction: acrylic acid (AA) grafting and attachment of a peptide with an arginine–glutamic acid–aspartic acid–valine (REDV) sequence. The study examined the correlation between the concentration of modifying agents (AA and peptide) in the modifying solution and the number of endothelial cells that adhered to the modified surfaces. Chemical analysis (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy) confirmed the presence of surface-bonded peptides on the modified materials. The applied coating significantly increased surface hydrophilicity (contact angle ≤ 60°). Introduction of the coating did not influence the activated partial thromboplastin time of plasma contacted with materials. The modification resulted in a significant decrease in the number of surface-adhered platelets (PU: 2·8%; modified materials: <0·5%) and a twofold decrease in the amount of surface-adsorbed fibrinogen. The relationship between the number of surface-adhered cells and the surface density of carboxyl (COOH) groups was demonstrated. The highest percentage of cell-occupied surface (>90%) was obtained for materials modified with 3% AA solution. The introduction of REDV promoted cell adhesion, although this effect strongly depended on the surface density of carboxyl groups.