Epidemiological studies suggest that a high dietary intake of flavanols, a subclass of flavonoids, is associated with reduced risk of vascular disease. Clinical studies have also shown that the consumption of certain flavanol-rich foods (e.g., cocoa, tea, red wine), as well as intake of the individual flavanol (-)-epicatechin, can result in improvement in a number of parameters associated with vascular disease, including improved endothelial function, reduced platelet reactivity, and reduced oxidative stress. The present study assessed the effects of a flavanol-rich supplement on platelet reactivity and plasma oxidant defense in a group of smokers, a population at an elevated risk for vascular disease. Male smokers were randomly assigned to a placebo (n = 10) or a flavanol-rich grapeseed extract (FRGSE; n = 13) group, and after an overnight fast, blood samples were collected before and at 1, 2, and 6 hours following consumption of the placebo or supplement. The FRGSE supplement, but not the placebo, significantly decreased ADP-stimulated platelet reactivity at 1, 2, and 6 hours following intake (P < .05) compared to baseline levels. Similarly, the supplement, but not the placebo, decreased epinephrine-stimulated platelet reactivity 2 hours following consumption. Plasma antioxidant capacity (total radical trapping antioxidant potential), lipid oxidation (plasma thiobarbituric acid-reactive substances), and serum uric acid concentrations were not affected in either group. Thus smokers may obtain some health benefits from the consumption of certain flavanol-rich foods, beverages, and supplements.