Interposition vein grafting is an important technique in microvascular free tissue transfer. Studies in rats have demonstrated that the patency rate of vessels is not affected by interposition grafting when the vein grafts and receipt vessels are of similar diameter. Size discrepancy between vein grafts and recipient vessels is frequently encountered in clinical practice and may potentially be an important factor in anastomotic patency. This study was, therefore, designed to assess the effect of vein graft diameter on the patency of arterial repair and survival of a groin free flap in the rat model. Forty-nine Sprague-Dawley rats were used. The inferior epigastric and femoral veins were used to reconstruct the femoral artery in situ (12 rats, 24 anastomoses) and in groin free flaps (30 rats). The vessel patency with inferior epigastric (1:1 size match) and femoral (2:1 size match) veins was 100% in the non free flap model. In the free flap model, flap survival was 30% in the femoral (2:1 size match) vein graft group. This was significantly less than both the free flap epigastric vein graft group (90% survival) and primary anastomoses group (100% survival). The results of this study suggest that size-matched interposition vein grafts can provide a high degree of reliability, but with size mismatch vein grafts are prone to thrombus formation and subsequent free flap failure.