Many engineers and surgeons trace implant failure to poor osseointegration (or the bonding of an orthopedic implant to juxtaposed bone) and/or bacteria infection. By using novel nanotopographies, researchers have shown that nanostructured ceramics, carbon fibers, polymers, metals, and composites enhance osteoblast adhesion and calcium/phosphate mineral deposition. However, the function of bacteria on materials with nanostructured surfaces remains largely uninvestigated. This is despite the fact that during normal surgical insertion of an orthopedic implant, bacteria from the patient's own skin and/or mucosa enters the wound site. These bacteria (namely, Staphylococcus epidermidis) irreversibly adhere to an implant surface while various physiological stresses induce alterations in the bacterial growth rate leading to biofilm formation. Because of their integral role in determining the success of orthopedic implants, the objective of this in vitro study was to examine the functions of (i) S. epidermidis and (ii) osteoblasts (or bone-forming cells) on ZnO and titania (TiO(2)), which possess nanostructured compared to microstructured surface features. ZnO is a well-known antimicrobial agent and TiO(2) readily forms on titanium once implanted. Results of this study provided the first evidence of decreased S. epidermidis adhesion on ZnO and TiO(2) with nanostructured when compared with microstructured surface features. Moreover, compared with microphase formulations, results of this study showed increased osteoblast adhesion, alkaline phosphatase activity, and calcium mineral deposition on nanophase ZnO and TiO(2). In this manner, this study suggests that nanophase ZnO and TiO(2) may reduce S. epidermidis adhesion and increase osteoblast functions necessary to promote the efficacy of orthopedic implants.