PURPOSE: Synthetic grafts have been increasingly used for complex vascular reconstructions in patients with limited autologous vein availability. Materials currently in use induce increased stenosis and graft thrombosis compared with autologous vein, especially in smaller vessels. We examined whether grafts constructed of a porous biodegradation-resistant polycarbonate polyurethane (PU) exert better biocompatibility in terms of faster endothelialization and decreased chronic proliferation of intimal cells compared with expanded polytetrafluoroethylene (ePTFE). METHODS: PU or ePTFE interposition grafts were implanted into the abdominal aortas of male Sprague-Dawley rats (PU, n = 37; ePTFE, n = 32). Grafts were removed at days 1, 7, 14, 28, and 56 and 6 months and were evaluated by immunohistochemical, electron microscopic, and morphometric techniques. Bromodeoxyuridine (BrdU) was injected at 1 and 24 hours before death to determine cellular proliferation. Endothelial cells and smooth muscle cells were identified with antibodies to von Willebrand factor and alpha-actin, respectively. RESULTS: The luminal surface of PU grafts took 4 weeks to completely endothelialize, whereas ePTFE grafts took 24 weeks (P <.05). Neointimal cell proliferation was lower in PU grafts compared with ePTFE at 56 days (1.4 +/- 0.1 versus 8.6 +/- 1.5, P <.001) and at 6 months (0.15 +/- 0.002 versus 3.4 +/- 0.5, p <.001). Neointimal thickness at 6 months after implantation was 3.2 +/- 0.8 micrometer for PU compared with 10.3 +/- 3.1 micrometer for ePTFE (P <.05). CONCLUSION: Polycarbonate polyurethane small vascular prostheses promoted faster luminal endothelialization, induced less chronic intimal proliferation, and produced a significantly thinner neointima than ePTFE grafts. These findings suggest that aliphatic-polycarbonate urethanes may offer advantages over standard materials such as ePTFE for vascular graft construction.