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Long-bone segmental defects caused by infection, fracture, or tumour are a challenge for orthopaedic surgeons. Structural allografts are sometimes used in their treatment but their poor biological characteristics are a liability. The objective of this study was to determine whether the addition of recombinant vascular endothelial growth factor-A (VEGF) to a structural allograft improved its integration into a rabbit tibial segmental defect in a non-union model. Tibial segmental defects were filled with heat sterilized allogenic tubular tibiae sections and then stabilized with a screw plate. In the VEGF treatment group (n = 6 tibiae), 2 μg of VEGF added to a 50 μl matrigel solution was inserted into the allograft cavity. In the control group (n = 6 tibiae), only matrigel was added. After 12 weeks, macroscopic and microscopic analysis, radiographs, and computerized micro-tomography (micro-CT) were performed. If allograft consolidation was present, a torsional resistance analysis was performed. Addition of VEGF to the allograft decreased the rate of osteosynthesis failure compared with the control group (1/6 vs. 5/6, p = 0.08), increased trabecular continuity evaluated by micro-CT in the bone–allograft interphases (8/12 vs. 2/12, p = 0.036) and histological trabecular continuity (7/12 vs. 0/12, p = 0.0046). Full consolidation was observed in three tibiae of the VEGF group and one in the control group (differences not significant); however, torsional resistance showed no significant differences (n.s.). Addition of VEGF to a structural allograph inserted into a rabbit tibial segmental defect increased allograft integration rate. Further research in this direction might help clinicians in dealing with large bone defects.