Infection associated with biomaterials used for orthopedic prostheses remains a serious complication in orthopedics, especially tumor surgery. Silver-coating of orthopedic (mega)prostheses proved its efficiency in reducing infections but has been limited to surface areas exposed to soft tissues due to concerns of silver inhibiting osseous integration of cementless stems. To close this gap in the bactericidal capacity of silver-coated orthopedic prostheses extension of the silver-coating on surface areas intended for osseous integration seems to be inevitable. Our study reports about a PVD- (physical-vapor-deposition-) silver-coated cementless stem in a canine model for the first time and showed osseous integration of a silver-coated titanium surface in vivo. Radiological, histological, and biomechanical analysis revealed a stable osseous integration of four of nine stems implanted. Silver trace elemental concentrations in serum did not exceed 1.82 parts per billion (ppb) and can be considered as nontoxic. Changes in liver and kidney functions associated with the silver-coating could be excluded by blood chemistry analysis. This was in accordance with very limited metal displacement from coated surfaces observed by laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) 12 months after implantation. In conclusion our results represent a step towards complete bactericidal silver-coating of orthopedic prostheses.