Objectives: Increased hemodynamic stress on vein grafts used in the arterial system is associated with vein graft disease. We determined whether a novel biodegradable external mesh stent could inhibit medial–intimal hyperplasia by suppressing hemodynamic stress on vein grafts and improve long-term patency. Methods: Twenty-four beagles underwent bilateral femoral interposition grafting using reversed femoral veins. Vein grafts were externally supported by a novel poly l-lactide-ε-caprolactone copolymer (P(LA/CL)) biodegradable mesh stent or a nonabsorbable mesh stent. Vein grafts with no reinforcement were used as controls. The grafts were harvested 6 and 12 months after implantation for morphometric and immunohistochemical assessment. Results: The endoluminal circumferential vein graft length was smaller in the P(LA/CL) and nonabsorbable groups (17.2 ± 2.9 and 19.0 ± 0.3 mm, respectively), than that in the control group (25.0 ± 2.6 mm, P &lt
 0.01) at 12 months. The mean intimal–medial thickness was thinner in P(LA/CL) and nonabsorbable stent groups (0.18 ± 0.05 and 0.16 ± 0.05 mm, respectively), than that in the control group (0.30 ± 0.08 mm, P &lt
 0.01). Differences in the intimal–medial thickness among the groups were associated with the magnitude of cellular proliferating activity. The graft patency ratio (100 %) was higher in the P(LA/CL) group than that in the nonabsorbable and control groups (72.2 and 63.6 %, respectively, P &lt
 0.05). Conclusions: The biodegradable P(LA/CL) external mesh stent improved vein graft patency for 12 months and prevented vein graft dilatation and intimal hyperplasia associated with suppressed neointimal layer cellular proliferating activity.