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To evaluate the effect of vascular endothelial growth factor (VEGF) on full-thickness skin graft (FTSG) survival on irradiated tissue as a model of wound healing in ischemic conditions.Twenty-four Sprague-Dawley rats underwent 30 Gy of irradiation to their left dorsum (10 Gy/d). After 4 weeks of recovery, 3-cm FTSGs were harvested from the healthy contralateral dorsum and placed onto irradiated recipient beds. Before grafting, recipient beds were delivered subfascial injections of either VEGF protein (5 μg) or physiologic saline. Graft failure (more than 10% necrosis) and graft microvascular density were compared between groups.Seven of the 11 FTSGs from saline-treated irradiated beds (64%) failed, whereas the failure rate for grafts treated with VEGF was 23% (3 of 13) (P = .048). Mean microvascular density was not different between groups.Exogenously administered VEGF may improve the outcome of FTSGs on irradiated tissue beds.