The development of small-diameter vascular grafts requires testing in large animal models before advancing to clinical trials. Vascular graft interposition implantation in sheep carotid arteries (CAs) is the most widely used model, but ovine CAs are prone to severe spasm following surgical manipulation, potentially impairing graft performance assessment. There is a paucity in the literature on reducing sheep CA spasm using effective vasodilator therapeutic protocols. In this study, four healthy Merino cross White Suffolk wethers (1-2 years, 52.1 ± 0.8 kg) underwent CT angiography and CA graft surgery. CT angiography using iodinated contrast agent was performed with innominate artery access via the CA or ascending aortic arch access via the femoral artery. Sheep were randomly allocated to then underwent right CA sham surgery or left CA vascular graft implantation. A variety of vasodilators, including papaverine, sodium nitroprusside, verapamil and their combination, were tested for preventing or treating CA spasms intraoperatively. Blood flow was reassessed immediately after CA surgery using CT angiography. The results showed that innominate artery access via the CA for CT angiography in sheep induced pre-surgical CA spasm with reduced arterial flow. Conversely, ascending aortic arch access via the femoral artery for CT angiography did not cause CA spasm and maintained arterial flow. During CA graft surgery, surgical trauma induced CA spasm, which was prevented by localised intraarterial administration of vasodilators papaverine hydrochloride and verapamil prior to significant surgical manipulation.