Current vascular access options require frequent interventions. In situ tissue engineering may overcome these limitations by combining the initial success of synthetic grafts with the long‐term advantages of autologous vessels by using biodegradable grafts that transform into autologous vascular tissue at the site of implantation. Scaffolds(6mm‐Ø) made of supramolecular polycarbonate‐bisurea(PC‐BU), with a polycaprolactone(PCL) anti‐kinking‐coil, were implanted between the carotid artery and jugular vein in goats. A subset was bio‐functionalized using bisurea‐modified‐SDF1α‐derived peptides and ePTFE grafts as controls. Patency was monitored monthly. Grafts were explanted after 1 and 3 months, and evaluated for material degradation, tissue formation, compliance, and patency. At 3 months, the scaffold was resorbed and replaced by, and vascular neo‐tissue, including elastin, contractile markers an endothelial lining. No dilations, ruptures, or aneurysms were observed and grafts were successfully cannulated at termination. SDF1α‐peptide‐biofunctionalization did not influence outcomes. Patency was lower in the TE grafts(50%) compared to controls(100% patency), predominantly caused by intimal hyperplasia. We demonstrated the rapid remodeling of a synthetic, biodegradable vascular scaffold into a living, compliant arteriovenous fistula in a large animal model. Despite lower patency compared to ePTFE, this transformation into autologous and compliant living tissue with self‐healing capacity may have long‐term advantages.This article is protected by copyright. All rights reserved