This study presents the synthesis and evaluation of cell adhesive poly(ethylene oxide) (PEO) star polymers for potential biomedical applications. Star polymers with a size of approximately 20 nm and with relatively low polydispersities (M(w)/M(n) ≤ 1.6), containing GRGDS (Gly-Arg-Gly-Asp-Ser) segments, were prepared by atom transfer radical copolymerization of PEO methyl ether methacrylate macromonomer (MM), telechelic GRGDS-PEO-acrylate MM, and ethylene glycol dimethacrylate (EGDMA). Results from (1)H NMR spectroscopy confirmed the covalent incorporation of the peptide into the star periphery. In vitro cytotoxicity experiments showed star polymers to be cytocompatible (≥95% cell viability) and GRGDS-star hybrid hydrogels supported the attachment of MC3T3.E1 (subclone 4) cells. Hybrid hydrogels were prepared by free radical photopolymerization based on 10% (wt/v) PEO dimethacrylates M(n) = 4000 g/mol with 1% (wt/v) GRGDS-star polymers having different peptide content. Cell adhesiveness was also determined from thin film coatings prepared with GRGDS-containing star polymers on nonadherent plastic plates. After 24 h incubation, phase contrast microscopy and scanning electron microscopy (SEM) images showed uniform cell adhesion and distribution over the film containing cell-adhesive star polymers. These results confirm that incorporation of RGD ligand-binding motifs into PEO-based star polymers is required to influence substrate-cell interactions.