Although the current percutaneous osseointegrated (OI) prosthetic attachment systems are novel clinical treatments for patients with limb loss, there have only been limited translational studies undertaken to date. To bridge this knowledge gap, from a larger study group of 86 animals that were implanted with a novel percutaneous OI implant construct, 33 sheep were randomly selected from the 0-, 3-, 6-, 9-and 12-month groups for histomorphometric analyses of periprosthetic cortical bone tissue. At necropsy, implanted and nonimplanted limbs were harvested and processed for the evaluation of cortical bone porosity and mineral apposition rate (MAR). The data showed a maximum increase in bone porosity within the first 3 months following implantation and then a progressive reduction in porosity to the baseline steady-state (''Time 0'') value by 12 months. The data further verified that the MAR increased during the first 6 months of implantation, reaching a plateau between 6 and 9 months, followed by a progressive decline to the baseline steady state. It was concluded that clinical load bearing and falls precautions, taken during the first 3-6 months following percutaneous OI device implantation surgery, could greatly limit bone fractures during this vulnerable time of increasing cortical bone porosity. Anat Rec, 295:1437Rec, 295: -1445Rec, 295: , 2012. V C 2012 Wiley Periodicals, Inc. † Key words: percutaneous osseointegrated prosthesis; sheep amputation model; mineral apposition rate; porosity; back-scattered electron imagingOver the past two decades, the percutaneous osseointegrated (OI) skeletal docking of artificial limbs has been introduced as an alternative to the historic sockettype prosthetic attachment systems for patients with limb loss. As this OI system allows ground reaction forces to be directly transmitted to the skeletal system, it improves gait symmetry, allows osseoperception, and increases prosthesis comfort and wear-time for the patient (Hagberg et al