Nanoporous polyethersulfone (PES) membranes are widely used in dialysis systems due to their permeability and diffusion characteristics. However, PES membranes lack blood compatibility, which influences their permeability performance when employed in blood contact devices. Parylene film was deposited on a PES membrane surface and the membrane permeability and blood compatibility were investigated by long-term blood diffusion testing. After 28 days of testing, 90% of a bare PES membrane was covered with platelets, while the parylene film coated PES membrane had improved biocompatibility with a platelet coverage of only 20–30%. The permeability of the bare PES membrane significantly declined during the first 7 days of the blood diffusion and became stable after 8 days. In contrast, the permeability of the parylene film coated PES membrane exhibited more consistent performance during the entire test. Thus, parylene film coating on PES membrane has potential for application in hemodialysis systems. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 40024.