We developed small-diameter vascular grafts made of slow degradable poly(e-caprolactone) nanofibres obtained by electrospinning. The process was optimized by a factorial design approach. Fibre sizes, graft morphology, and the resulting tensile stress and tensile strain values were studied as a function of various parameters in order to obtain optimal vascular grafts for implantation after gamma sterilization. Consequently, these grafts were implanted as an abdominal aortic or carotid substitute in more than 100 animals (rats and pigs) for periods up to 2-years showing no aneurysms, better patency, compliance and biocompatibility with faster endothelialization, less intimal hyperplasia and calcification compared to the clinically used ePTFE graft after long-term implantation in the rat aorta. Despite degradation, our graft maintains good mechanical characteristics, growth potential, and tissue regeneration with specific cells, adequate angiogenesis and extra-cellular matrix formation. Thus, such a novel in situ tissue-engineered graft using the body as bio-reactor, may become better, shelf-ready, cheaper and clinically widely applicable for cardiovascular revascularization procedures.