The study objective was to determine safety and efficacy of a treated bovine vascular xenograft, in two Good Laboratory Practice compliant studies in sheep following carotid graft implantation. In one study, a 3- to 5-mm diameter xenograft was implanted into the right carotid artery of male sheep and compared to autologous jugular vein and a polymeric grafts similarly implanted. In a second study, a 9.5- to 14-mm diameter xenograft similarly implanted into the right carotid artery was compared to an autologous saphenous vein. Monthly Doppler ultrasound evaluation of implant patency and flow in implants and contralateral control carotid arteries was performed. The small vessel cohort 6 month xenograft patency was equivalent (or better) than animals with polymeric vascular graft or autologous vein implants; the aneurysm incidence was less than that of autologous vein grafts. In the large vessel cohort, all 15 xenografts and 12/15 saphenous vein implants were patent at 6 month follow-up. Tissue histology showed mild inflammatory responses in the xenografts that was slightly greater than suture material. In summary, treated bovine xenograft performance in this small study suggests it may be superior to polymeric autologous vein grafts, and may have a similar failure rate as autologous vein grafts after implantation.