Because of the severe increase of mortality by cardiovascular diseases, there has been rising interest among the tissue-engineering community for small-sized blood vessel substitutes. Here we present small diameter vascular grafts made of slow degradable poly(epsilon-caprolactone) nanofibers obtained by electrospinning. The process was optimized by a factorial design approach that led to reproducible grafts with inner diameters of 2 and 4 mm, respectively. Fiber 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. The influence of polymer concentration, solvent, needle-collector distance, applied voltage, flow rate, and spinning time has been studied. Consequently, an optimized vascular graft was implanted as an abdominal aortic substitute in nine rats for a feasibility study. Results are given following up a 12-week implantation period showing good patency, endothelization, and cell ingrowth.