Hydrogel coatings have been widely researched as a nonfouling surface modification of materials for cardiovascular applications. In this study, we examined cell-surface interactions between a poly(acrylamide-copolyethylene glycol/acrylic acid) interpenetrating network (IPN) hydrogel and aortic endothelial cells (ECs). The IPN was covalently attached to polystyrene to form a nanometer scale thick hydrogel, and the IPN layer was activated by conjugation of the cell adhesion peptide Arg-Gly-Asp (RGD). On IPN surfaces lacking the RGD peptide, EC did not adhere and spread even after long-term incubation. The IPN was able to support greater EC adhesion and spreading with increasing RGD surface concentrations. Upon adequate adhesion and spreading, ECs migrated and proliferated at high rates regardless of the RGD surface concentration. These results suggest that this IPN can be used to promote endothelialization of vascular implants made of polymeric and metal materials for cardiovascular applications.