A prosthetic vascular graft that induces perigraft tissue incorporation may effectively prevent serious sequelae such as seroma formation and infection. Radiation-crosslinked gelatin hydrogel (RXgel) mimics the chemical and physical properties of the in vivo extracellular matrix and may facilitate wound healing by promoting tissue organization. Fibroblasts cultured on RXgel actively migrated into the gel for up to 7 days. RXgels of three different degrees of hardness (Rx[10], soft; Rx[15], middle; Rx[20], hard) were prepared, and small disc-like samples of RXgels were implanted into rats. In vitro and in vivo results indicated that Rx[10] was too soft to coat vascular grafts. Thus, expanded polytetrafluoroethylene (ePTFE) vascular grafts coated with RXgel were developed using Rx[15] and Rx[20] gels, and ring-shaped slices of the graft were implanted into rats. Alpha-smooth muscle actin (SMA) and type III collagen (Col-III) levels were detected by immunohistochemistry. Immunohistochemical staining for SMA and Col-III demonstrated that RXgel-coated vascular grafts induced more granulation tissue than non-coated grafts on days 14 and 28 after implantation. RXgel-coated ePTFE vascular grafts may provide a solution for patients by reducing poor perigraft tissue incorporation.