This ex vivo study is aimed at determining the beneficial effects of antioxidant agents on human saphenous vein endothelial function. Vein rings harvested during infrainguinal bypass surgery were assessed in an organ bath for endothelium-dependent relaxation, initially without and then with the addition of 10 μM manganese tetrakis benzoic acid porphyrin (MnTBAP), 0.01% N-acetylcysteine (NAC), 0.02% NAC, 10 μM vitamin C, and 100 μM vitamin C. Fifty-five vein rings from 22 patients were analyzed. MnTBAP improved the endothelium-dependent relaxation when compared with control (57.0% vs 37.8%, P < .01). Addition of 0.01% or 0.02% NAC did not improve the endothelium-dependent vasorelaxation (28.2% vs 18.6%, P = ns and 37.8% vs 29.8%, P = ns, respectively). Although 10-μM vitamin C failed to improve endothelial function (50.6% vs 37.2%, P = ns), 100-μM vitamin C significantly enhanced endothelium-dependent relaxation (66.5% vs 38.3%, P < .001). These results suggest that the addition of MnTBAP and high-dose vitamin C can improve the endothelial function of harvested saphenous vein segments in an ex vivo model.