In this study, a random copolymer of poly(vinyl pyrrolidone-co-methyl methacrylate-co-acrylic acid) was synthesized via a one-pot reaction with the reversible addition-fragmentation chain-transfer method and was then blended with poly(ether sulfone) (PES) to prepare flat-sheet membranes that were expected to have anticoagulant and antifouling properties. The synthesized copolymer was characterized by Fourier transform infrared (FTIR) and NMR spectroscopy. The molecular weights and molecular weight distributions were determined by gel permeation chromatography. Elemental analysis was used to calculate the molar ratios of vinyl pyrrolidone (VP), methyl methacrylate (MMA), and acrylic acid (AA) in the copolymer. A liquid-liquid phase-inversion technique was used to prepare the copolymer-blended PES membranes. X-ray photoelectron spectroscopy and attenuated total reflectance-FTIR spectroscopy were used to investigate the copolymer on the membrane surfaces. Compared with the pristine PES membrane, the modified PES membranes showed improved hydrophilicity, low hemolysis ratios, decreased protein adsorption, and suppressed platelet adhesion. Furthermore, the thrombin time and activated partial thromboplastin time indicated that the blood compatibility of the modified PES membranes were improved. The results of the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the cell morphology suggested that the cytocompatibility increased. In addition, the modified membranes showed good protein antifouling properties. (c) 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4284-4298, 2013