Tissue regeneration may enhance long term performance of vascular grafts. The objective was to manufacture vascular grafts of porcine small intestine submucosa (SIS) and evaluate their permeability, biocompatibility and mechanical properties in an animal model. Methods SIS layers were obtained, grafts (5mm diameter) were manufactured with layers of SIS, dehydrated and sterilized. A graft was implanted on a newborn bovine subject, with an end-to-end anastomosis in the internal carotid artery. The animal was observed for 45 days, euthanized and the implant and adjacent carotid artery were removed and subjected to histological analysis and mechanical tensile test in the longitudinal direction. Results Nonimplanted, dry grafts (n=5) had a rupture load of 37±15 N and a rupture stress of 15±6 MPa. Ultrasound examinations of the implanted graft showed permeability. Tissue regeneration of the explanted graft was evidenced by vascularization, proliferation of myocites and fibroblasts. A small thrombus was present on the internal graft wall.The implanted graft had a rupture load of 16 N and a rupture stress of 0.5 MPa. The carotid artery had a rupture load of 7.8 N and a rupture stress of 1.5 MPa. The SIS vascular graft demonstrated permeability, biocompatibility and evidence of tissue regeneration. Mechanical tests indicate that it has an adequate performance under physiological conditions, compared to the native artery. Superficial treatments of the graft are being studied to inhibit thrombus formation.