A segmental tibial defect model in a large animal can provide a basis for testing materials and techniques for use in nonunions and severe trauma. This study reports the rationale behind establishing such a model and its design and conclusions. After ethics approval of the study, aged ewes (older than 5 y; n = 12) were enrolled. A 5-cm mid diaphyseal osteoperiosteal defect was made in the left tibia and was stabilized by using an 8-mm stainless-steel cross-locked intramedullary nail. Sheep were euthanized at 12 wk after surgery and evaluated by using radiography, microCT, and soft-tissue histology techniques. Radiology confirmed a lack of hard tissue callus bridging across the defect. Volumetric analysis based on microCT showed bone growth across the 16.5 cm(3) defect of 1.82 ± 0.94 cm(3). Histologic sections of the bridging tissues revealed callus originating from both the periosteal and endosteal surfaces, with fibrous tissue completing the bridging in all instances. Immunohistochemistry was used to evaluate the quality of the healing response. Clinical, radiographic, and histologic union was not achieved by 12 wk. This model may be effective for the investigation of surgical techniques and healing adjuncts for nonunion cases, where severe traumatic injury has led to significant bone loss.