Background: Prosthetic vascular graft infection is an unsolved fatal complication after aortic surgery. We hypothesized that increased vascularity around a prosthetic graft may exert a preventive role against bacterial infection. Methods: Eighty-three Fischer rats were divided into five groups according to the types of subcutaneously implanted prosthetic graft and granulocyte-colony stimulating factor (G-CSF) treatment. The groups G and C had gelatin hydrogel microspheres-incorporated graft (gel graft) with or without concomitant systemic administration of G-CSF (50 μg/kg), respectively. The groups FG and F had the gel graft impregnated with 100 μg of basic fibroblast growth factor (bFGF) with or without systemic G-CSF. The group N received untreated grafts. Seven days after graft implantation, broth containing methicillin-sensitive Staphylococcus aureus (4.0 × 103 colony-forming units) was inoculated onto the graft. All the grafts and the surrounding tissues were explanted 2 days later. Quantitative culture for methicillin-sensitive Staphylococcus aureus from the grafts and histologic assessment for capillary number in the tissue were performed. Results: Positive infection rates in the groups N, C, and G were 34.7%, 30.4%, and 15.3%, respectively; whereas those were zero in the F and FG groups. Tissue around the grafts demonstrated significantly higher number of capillaries in the groups F and FG compared with the groups C and G. The number of bacterial colonies inversely correlated with the number of capillaries around the implanted graft (r = -0.32, p < 0.05). Conclusions: Basic fibroblast growth factor incorporated into a prosthetic graft with or without systemic G-CSF can induce angiogenesis around the graft and prevent prosthetic graft infection.