A self-sealing vascular graft, including a substrate with a sealant layer and several optional additional layers, is described. The substrate can be ePTFE and the material used for the sealant and additional layers can be polyurethane. The sealant layer and additional layers may include one or more base layers, one or more foam layers, beading of different sizes and shapes, and ePTFE tape. A flared cuff may be integral to one or both ends of the substrate or may be attached to one or both ends. Various methods of making a self-sealing vascular graft are also described, including methods of disposition, methods of forming, methods of bonding and methods of attaching.