SUMMARYAims: Ginseng root and its derivatives remain atop the most widely used medicinal herbs in cardiovascular disease, despite inadequate substantiation of efficacy. We previously reported the potential of Korean red ginseng (KRG) to affect vascular tone by decreasing arterial wave reflection via an unknown mechanism. Given the preclinical link between ginseng intake and vasoactivity related to nitric oxide (NO) production, we sought to directly evaluate the effects of KRG root and its major root components, on an established noninvasive measure of endothelial function. Methods: In an acute, randomized, placebocontrolled, double-blind, crossover design, 16 healthy participants (9M:7F, age:30 AE 9y, BMI: 24 kg AE3 kg/m 2 , systolicBP/diastolicBP: 109 AE 11/66 AE 8 mmHg) on four occasions were administered: KRG root (3 g), KRG ginsenosides extract, KRG polysaccharides extract, and cornstarch control. Extracted fractions were delivered at doses bioequivalent to those found in 3 g of KRG. Flow-mediated vasodilatation (FMD) assessment, preceding a brachial blood pressure measurement, was performed at baseline and at 90 and 180 min posttreatment to assess endothelial function. Results: KRG significantly improved FMD posttreatment. Maximal vasodilatation of D2.57 AE 2.8% occurred at 180 min compared with control (DÀ0.83 AE 2.7%, P = 0.003 for all comparisons). The ginsenoside extract produced a comparable response (D1.75 AE 2.6%), but not the polysaccharide fraction (D0.10 AE 2.7%). Brachial blood pressure remained unchanged for all treatments (P = 0.45). Conclusions: KRG acutely improved endothelial function in healthy individuals, which appears to be attributable to its ginsenoside containing fraction. Our data confirm preclinical data and support the potential for these compounds as targets for therapeutic strategies in disorders involving endothelial dysfunction.