Purpose: The aim of this study was to investigate the cellular response of human gingival fibroblasts (HGFs) cultured on smooth or rough zirconia (Zr) or titanium (Ti) disks. Materials and Methods: Disks fabricated from four different materials-smooth Zr (Zr-S), rough Zr (Zr-R), smooth Ti (Ti-S), and rough Ti (Ti-R)-were used, and surface roughness was analyzed by atomic force microscopy. After HGFs were cultured on these disks, cell morphology was examined by scanning electron microscopy, cell proliferation activity was evaluated by a monotetrazolium assay, and gene expression levels of various collagens and integrins were measured by real-time polymerase chain reaction. Results: The Ti-R disks were the roughest, followed by Zr-R, Ti-S, and Zr-S, in that order. The cells cultured on the Zr-S and Ti-S disks appeared to be more aligned with the fine irregularities at later time points, whereas the cells cultured on the Zr-S showed the weakest spreading compared to the other surfaces after 3 hours of culture. With respect to proliferation, cells proliferated significantly faster on the Zr-S surface than on the other surfaces. Gene expression of integrin α2 at 3 hours and integrin α5 and type I collagen at 48 hours on Zr-S was significantly up-regulated compared to Ti. Conversely, the expression of integrins ß1 and ß3 and type III collagen was significantly decreased on Zr-S at 1 hour compared to the other materials. Conclusion: These data indicate that different surface materials and topographies may induce a distinct HGF morphology, proliferation, and gene expression. Keywords: fibroblasts, gene expression, integrins, titanium, zirconia