The effects on cell adhesion induced by changes in the topography and chemistry of poly(2- hydroxyethyl methacrylate) hydrogel surfaces were investigated in vitro using the human corneal epithelial cell line, HCE-T. Poly(2-hydroxyethyl methacrylate) surfaces with a lotusleaf-like topography and poly(2-hydroxyethyl methacrylate) surfaces with a flat topography, but functionalized with the cell-adhesive peptide sequence Arg–Gly–Asp, both enhanced attachment of HCE-T cells as compared to flat, non-functionalized poly(2-hydroxyethyl methacrylate) surfaces. However, the simultaneous existence on the same poly(2-hydroxyethyl methacrylate) surface of Arg–Gly–Asp motifs and of lotus-leaf-like topographical patterns led to an apparently antagonistic effect reflected in reduced cell attachment. The study provided additional evidence of the complexity of the cell–biomaterial interactions.