Background : Although platelets activation at sites of vascular injury is essential for hemostatic plug formation and vessel wall repair, they also play a harmful role in the pathogenesis of cardiovascular diseases (CVD) such as thrombosis, atherosclerosis and restenosis. Hypercholesterolemia is the critical step in the initiation of atherosclerosis, pacing hypercholesterolemic individuals at a greater risk for CVD. The amount of cholesterol found within the arterial wall and the membranes of platelets is proportional to the serum cholesterol level and can directly and indirectly influence the rate of atherosclerosis development. Methods : In this study, we examined whether the daily consumption of Korean red ginseng-water extract (KRG-WE) could prevent the hypercholesterolemia-enhanced platelet the hypercholesterolemia-enhanced platelet aggregation and progression of hypercholesterolemic atherosclerosis in high-cholesterol-fed rabbit, an animal model for hypercholesterolemia in vivo with four groups of rabbits (normal diet, high cholesterol diet, KRG-WE treated and lovastatin treated) for 4 weeks. Results : In this experiment, dietary supplementation with KRG-WE and lovastatin reduced the blood cholesterol levels (total cholesterol, LDL cholesterol and triglyceride, but not HDL cholesterol) and formation of atheromatous lesions in 0.5% cholesterol diet-induced hypercholesterolemic rabbit model. In addition, KRG-WE administration potently inhibited platelet aggregation induced by low doses of agonists (0.5 μg/mL collagen and 0.025 unit/mL thrombin) with inhibition percentages of 98% and 54%, respectively. Discussion : In conclusion, daily consumption of KRG-WE could be a useful alternative measure for the prevention of thrombus and atheroma formation in hypercholesterolemia.