Alpha-lipoic acid (ALA) immobilized polysulfone (PSF) hemodialysis membranes have been fabricated by the dry–wet phase inversion technique. The antioxidant properties of the membranes were evaluated in terms of inhibition of reactive oxygen species (ROS) in blood plasma, while their blood compatibilities were determined by quantitating plasma protein adsorption, platelet adhesion, activation and cytotoxicity to blood cells. The stability of ALA under typical hemodialysis conditions was improved by immobilization, and the greatest enhancement was achieved when it was sandwiched between two polyethyleneimine (PEI) layers. In vitro antioxidant activity measurements showed that ALA coated membranes are not only capable of reducing ROS levels in blood, protein adsorption and platelet activation on the membranes, but, can also prolong coagulation time. All membranes prepared were noncytotoxic to peripheral blood mononuclear cells. In addition, the high permeation rates of solutes through PSF membrane were not affected by ALA immobilization.