A major emphasis in biomaterials research is the design of the implant surface because of its profound influence on the tissue response. Many clinically used implants attempt to improve the tissue response through surface treatments. These physical or chemical modifications are known to alter the biological events at the tissue-implant interface. Recent advances in nano-fabrication offer the ability to create novel 3D surface structures at the molecular scale. The nano-fabrication technique selected was electrochemical anodization. We anodized titanium (Ti) implants to form vertically aligned titanium dioxide (TiO2) nanotube arrays. The nanotubes had precisely controlled dimensions with diameters of either 30 nm or 100 nm with a 3:1 height to diameter aspect ratio. The controls used were micron-roughened titanium or chemically inert surfaces. This dissertation investigated the in vivo tissue response to these nano-modified implant surface modifications. First, the in vivo soft tissue response was measured by fibrotic capsule thickness and nitric oxide presence. These inflammatory parameters were significantly lower for TiO2 nanotubes surface compared with the titanium control. Second, the in vivo bone response was investigated histologically for bone-implant- contact area, and mechanically with a tensile pull-out test to quantify the interfacial adhesion force. TiO2 nanotubes exhibited close contact with bone, and increased the interfacial adhesion strength by approximately 9-fold compared with a Ti micron roughened control surface. Lastly, we modified the structure and chemistry of the nanotube surface to examine how these factors influence adhesion to bone. The TiO2 100 nm diameter nanotube increased bone adhesion by approximately 1-fold compared with the TiO2 30 nm diameter nanotube and by approximately 6-fold compared to the chemically inert 100 nm diameter nanotube surface. The increased bone adhesion observed on the TiO2 nanotube surfaces is thus dependent on both the nanotube structure and chemistry. These findings may be significant for the interaction between implants in soft tissue as well as bone tissue to improve future clinical implants.