Interposition grafts are an important and invaluable technique in free microvascular tissue transfer as they extend the vascular pedicle to allow it to reach undisturbed donor vessels away from the surgical or traumatic site. Autologous vein has been the most commonly used material for interposition grafting, but it has significant disadvantages. Nonautologous grafts are readily available and could certainly remedy most of the autologous graft disadvantages. This study was designed to (1) evaluate the patency of expanded polytetrafluoroethylene (PTFE) grafts in a simple microvascular vessel repair and (2) evaluate the survival of microvascular free flaps using PTFE arterial interposition grafts. The inferior epigastric vein or PTFE was used to reconstruct the femoral artery in 10 animals (20 sides) in a simple vessel repair model and in 20 animals in a groin free flap model. All epigastric vein grafts were patent at 1 week in the vessel repair group. Only five in the PTFE vessel repairs were patent. Nine of 10 free flaps were viable in the free flap group with epigastric vein interposition. All of the 10 free flaps with PTFE interposition failed. There was a statistically significant difference in vessel patency between PTFE grafts in the vessel repair and free flap models. Our data show that PTFE microvascular grafts are a poor substitute for vein grafts in the vessel repair and free flap animal models. We also found that simple vessel repair is not an acceptable model to study manipulations intended for free tissue transfer.