Objective: The present study compared the effects of local alendronate application on the osteogenesis of autogenous and xenogenous onlay grafts implanted in rabbit mandibles. Material and Methods: 28 New Zealand rabbits were used in this experimental animal study. The animals were randomly divided into 4 groups according to graft material as follows: D1: autogenous graft-saline; D2: 60% autogenous graft-40% alendronate D3: xenogenous bone graft-saline; D4: 60% xenogenous graft-40% alendronate. 3 histologic parameters were evaluated: the ratio of new bone formation to the total defect area, the active osteoblast-lined bone length, and the ratio of osteocyte-filled lacunae to total lacunae. At the same time, the grafted zones were evaluated using dual-energy X-ray absorptiometry (DEXA) and the Bone mineral density scores were measured. Results: The present study showed better results for the group receiving alendronate applied to autogenous graft when compared to other groups. Discussion: The administration of alendronate increases the resistance of autogenous graft; it may also enhance new bone formation and increase the viability of xenograft. Further animal studies supported with biomechanical tests are required prior to human studies.