The interactions between Arg-Gly-Asp (RGD) peptides and titanium oxide (TiO2) surfaces are of considerable interest to medical technological and fundamental researchers. In the present study, a molecular dynamics (MD) simulation was used to study the interfacial interaction between RGD and TiO2 at an atomistic level. Four important factors affecting RGD adsorption were considered: the initial configuration of the RGD, the crystal structure of the TiO2 materials, the presence of surface defects, and a water environment. Three types of RGD initial configurations were considered: lying and standing on the N or O end. First, RGD adsorptions on ideal rutile (110) and anatase (101) surfaces in a vacuum and in a water environment were studied; then the step edge effects were considered, and, finally, the synergistic effects of water and surface defects on RGD adsorption were investigated. The results from the vacuum indicated that the crystal structure of the surface was more important than the initial RGD configuration. The interaction between RGD and the anatase (101) surface was stronger than that between RGD and the rutile (110) surface according the energy analysis. Atomic step edges on TiO2 surfaces could greatly affect the adsorption of the RGD peptide. Water limited the interaction between the RGD peptide and the TiO2 substrate and helped to sustain the initial configuration of the former. These findings should be helpful in understanding the RGD–TiO2 interaction mechanisms and should provide useful theoretical guidelines for titanium surface treatments in orthopedic applications. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.