OBJECTIVES The goal of this study was to determine whether postprandial hyperglycemia, induced by oral glucose loading, attenuates endothelial function in healthy subjects without diabetes and whether coadministration of vitamins C and E could prevent these postprandial changes. BACKGROUND Epidemiologic evidence suggests that postprandial hyperglycemia, below diabetic levels, is a risk factor for cardiovascular disease. Postprandial hyperglycemia may promote atherosclerosis through endothelial dysfunction and oxidative stress. METHODS We evaluated the acute effects of oral glucose loading (75 g), alone and with vitamins C (2 g) and E (800 IU), on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery, in a randomized, double-blind, placebo-controlled, crossover study of 10 healthy volunteers. Changes in the levels of markers of oxidative stress (plasma malondialdehyde and erythrocyte glutathione, glutathione peroxidase and superoxide dismutase) were also assessed. RESULTS Increases in plasma glucose and insulin after glucose loading were unaffected by vitamin coadministration. With glucose loading alone, FMD fell from 6.5 ± 2.2 at baseline to 5.4 ± 1.7, 3.7 ± 2.1∗, 4.1 ± 3.5∗ and 5.7 ± 1.9% at 1, 2, 3 and 4 h (∗p < 0.05 vs. 0 h). In contrast, FMD did not change significantly after glucose plus vitamins (6.4 ± 1.3, 7.6 ± 1.8, 7.9 ± 2.7, 6.9 ± 2.3, 6.9 ± 1.9% at 0, 1, 2, 3 and 4 h). By two-way repeated measures analysis of variance we found a significant interaction between vitamin treatment and time (p = 0.0003), indicating that vitamins prevented the glucose-induced attenuation of FMD. Oxidative stress markers did not significantly change with glucose loading alone or with vitamins. CONCLUSIONS Oral glucose loading causes an acute, transient decrease of FMD in healthy subjects without diabetes, which is prevented by vitamins C and E.