Garlic and some of its organosulfur components have been found to be potent inhibitors of platelet aggregation in vitro. Demonstration of their efficacy in vivo, however, especially when administered over extended periods, is sparse. We recently performed a 10-month study comparing the effect of aged garlic extract (AGE) with placebo on the lipid profiles of moderately hypercholesterolemic men. In the course of the intervention trial, we examined platelet functions and susceptibility of lipoproteins to oxidation in a subgroup of this study population. Study subjects supplemented with 7.2 AGE per day showed a significant reduction of epinephrine- and, to a lesser degree, collagen-induced platelet aggregation but failed to demonstrate an inhibition of adenosine diphosphate (ADP)-induced aggregation. Platelet adhesion to fibrinogen, measured in a laminar flow chamber at moderately high shear rate, was reduced by ∼30% in subjects taking AGE compared with placebo supplement. A trend toward decreased susceptibility of lipoproteins to oxidation also was noted during AGE administration compared with the placebo period. We conclude that the beneficial effect of garlic preparations on lipids and blood pressure extends also to platelet function, thus providing a wider potential protection of the cardiovascular system.