This study investigates the potential of using endothelial progenitor cells (EPCs) to seed tissue-engineered small diameter blood vessels, specifically 4 mm grafts, to improve their patency and function. EPCs were isolated from peripheral blood of sheep, expanded ex vivo, and seeded onto decellularized porcine iliac vessels. The EPC-seeded grafts remained patent for up to 130 days in a sheep model, while non-seeded grafts occluded within 15 days. The EPC-seeded grafts exhibited contractile activity and nitric oxide-mediated vascular relaxation similar to native carotid arteries. These findings suggest that EPCs can function similarly to arterial endothelial cells, potentially improving the long-term survival of vascular grafts. The study also highlights the broader applications of EPCs in tissue engineering and treating vascular diseases due to their unique properties and ease of access.This study investigates the potential of using endothelial progenitor cells (EPCs) to seed tissue-engineered small diameter blood vessels, specifically 4 mm grafts, to improve their patency and function. EPCs were isolated from peripheral blood of sheep, expanded ex vivo, and seeded onto decellularized porcine iliac vessels. The EPC-seeded grafts remained patent for up to 130 days in a sheep model, while non-seeded grafts occluded within 15 days. The EPC-seeded grafts exhibited contractile activity and nitric oxide-mediated vascular relaxation similar to native carotid arteries. These findings suggest that EPCs can function similarly to arterial endothelial cells, potentially improving the long-term survival of vascular grafts. The study also highlights the broader applications of EPCs in tissue engineering and treating vascular diseases due to their unique properties and ease of access.