Limited incorporation and modest bone remodeling can cause allograft failure. We investigated whether mesenchymal stem cells (MSCs) and osteogenic protein-1 (OP-1) can improve allograft integration. A 3-cm full-size intercalary bone defect was created in the mid-diaphysis of the metatarsal bone of the sheep and it was replaced with an allograft alone (control group), or with MSCs (MSC group), OP-1 (OP-1 group), or MSCs and OP-1 (MSC + OP-1 group). Radiographic results showed a faster and complete integration of the allograft in the MSC + OP-1 group. Histology demonstrated that the amount of new bone was significantly greater inside the graft and a longer vessel penetration in the MSC + OP-1 group than in others. Mechanical strength of the allograft was not compromised by the high rate of bone remodeling. These results demonstrated that the association of MSCs and OP-1 improve bone allograft integration promoting an almost complete bone restoring.