Bone grafting procedures are widely used to repair large defects successfully in humans, but new surgical therapies can be designed to improve allograft integration. The objective of this study was to investigate the best surgical procedure to study bone graft integration in a large animal model. An osteoperiosteal defect of 3 cm in the tibia or in the metatarsal was made in 15 adult crossbreed sheep to investigate osteo-integration of a homologous bone graft in an intercalary critical defect. DCP plates, alone or in association with Scotchcast or external fixator were used as fixation devices. The Scotchcast as was applied after surgery and left for 2 months to avoid torsion stress of the limb during the stand up movement. Metatarsal defect fixed with 7-hole DCP plate and protected with Scotchcast was the best surgical approach to avoid early or late implant failures, and provided good radiographic results after 4 months.