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Over the past decade the increase of elderly population has determined a rise in the incidence of bone fractures, and the improvement of the implant–bone interface remains an open problem. Metal-organic chemical vapour deposition (MOCVD) has recently been proposed as a technique to coat orthopaedic and dental prostheses with metal nanostructured oxide films either through the decomposition of oxygenated compounds (single-source precursors) or the reaction of oxygen-free metal compounds with oxygenating agents. The present study was performed to assess the in vivo biocompatibility of commercially pure Ti (control material: TI/MA) implants (∅ 2 mm×5 mm length) coated with nanostructured TiO2 films by MOCVD (Ti/MOCVD) and then inserted into rabbit femoral cortical (middhiaphysis) and cancellous (distal epiphysis) bone. Histomorphometric, ultrastructural and microhardness investigations were carried out. Four and 12 weeks after surgery, significant (p<0.0005) increases in AI of Ti/MOCVD implants were observed as compared to Ti/MA implants (distal femoral epiphysis: 4 weeks=8.2%, ns; 12 weeks=52.3%, p<0.005; femoral diaphysis: 4 weeks=20.2%, p<0.0005; 12 weeks=10.7%, p<0.005). Bone microhardness results showed significant increases for the Ti/MOCVD versus Ti/MA implants at 200 μm in the femoral diaphysis (4 weeks=14.2, p<0.005) and distal femoral epiphysis (12 weeks=14.5, p<0.01) at 4 and 12 weeks, respectively. In conclusion, the current findings demonstrate that the nanostructured TiO2 coating positively affects the osseointegration rate of commercially pure Ti implants and the bone mineralization at the bone–biomaterial interface in both cortical and cancellous bone. [Copyright &y& Elsevier]