Evidence from infusion studies suggests that soy isoflavones influence nitric oxide-dependent vasorelaxation. It is uncertain whether orally consumed isoflavones have similar effects. Healthy postmenopausal women (n = 22) consumed 2 low-fat test meals in random order 1 wk apart, with 80 mg isoflavones (ISO) or without isoflavones (CON). Endothelium-dependent vasodilation, assessed by brachial artery flow-mediated dilatation (FMD), was measured in fasting subjects, and 4 and 6 h following the test meal, in addition to blood pressure and pulse wave analysis to derive the peripheral augmentation index (pAIx). Blood samples were taken after fasting, and 5 and 7 h following the test meal for serum isoflavone, plasma 8-isoprostane F(2alpha), nitric oxide metabolites (NOx), glucose, and triacylglycerol analysis. Serum genistein and daidzein concentrations (geometric mean, 95% CI) reached 1.49 (1.20-1.84) micromol/L and 0.95 (0.70-1.30) micromol/L, respectively, following ISO (7 h). FMD and plasma NOx concentrations were greater following ISO compared with CON, indicating better postprandial endothelial function. FMD values (%, mean +/- SD) were: CON, 5.49 +/- 2.32, 4.35 +/- 2.32, 4.40 +/- 2.26; ISO, 5.38 +/- 1.91, 5.08 +/- 1.74, 6.11 +/- 2.60, at baseline, 4 h, and 6 h, respectively (P < 0.01). Plasma NOx concentrations (micromol/L, mean +/- SD) were: CON, 20.0 +/- 5.1, 16.8 +/- 5.1, 23.1 +/- 6.0; ISO, 18.6 +/- 6.3, 19.5 +/- 5.1, 21.3 +/- 10.1, at baseline, 5 h, and 7 h, respectively (P < 0.005). Treatment did not affect pAIx, blood pressure, or plasma 8-isoprostane F(2alpha) concentrations. In conclusion, consuming an isoflavone-enriched low-fat meal acutely increases endothelium-dependent vasodilation in postmenopausal women. Regular consumption of soy isoflavones may protect against endothelial dysfunction.