BACKGROUND/OBJECTIVES@#Arterial stiffness and endothelial dysfunction are 2 of the independent predictors for cardiovascular disease, while Acanthopanax senticosus Harms (ASH) is a traditional medicinal plant that can improve cardiovascular health. This study aimed to investigate the efficacy of the fruit of ASH on vascular function in apparently healthy subjects. @*SUBJECTS/METHODS@#A 12-week, randomized, double-blind, placebo-controlled design, consisting of healthy adults with at least 2 of the following 3 conditions: borderline high blood pressure (BP; 120 mmHg ≤ systolic BP ≤ 160 mmHg or 80 mmHg ≤ diastolic BP ≤ 100 mmHg), smoking (≥10 cigarettes/day), and borderline blood lipid levels (220 ≤ total cholesterol ≤ 240, 130 ≤ low density lipoprotein cholesterol ≤ 165, or 150 ≤ triglyceride ≤ 220 mg/dL). Randomly assigned 76 subjects who received a placebo or 2 doses of ASH fruit (low, 500 mg/day; high, 1,000 mg/day) completed the intervention. Brachial-ankle pulse wave velocity (baPWV), flow-mediated dilation, carotid intima-media thickness, and BP were measured both at baseline and following the 12-week intervention. Endothelial nitric oxide synthase (eNOS) phosphorylation was assessed by western blotting. @*RESULTS@#Compared with the placebo group, the low-dose group showed more significant changes after the 12-week intervention period in terms of systolic BP (0.1 vs. −7.7 mmHg; P = 0.044), baPWV (31.3 vs. −98.7 cm/s; P = 0.007), and the ratio of phospho-eNOS/eNOS (0.8 vs. 1.22; P = 0.037). @*CONCLUSIONS@#These results suggest that ASH fruit extract at 500 mg/day has the potential to improve BP and arterial stiffness via endothelial eNOS activation in healthy adults with smoking and the tendency of having elevated BP or blood lipid parameters.