Background: Aqueous extracts from tomatoes display a range of antiplatelet activities in vitro. We previously showed that the active components also alter ex vivo platelet function in persons with a high response to ADP agonist. Objective: The objective was to evaluate the suitability of a tomato extract for use as a dietary supplement to prevent platelet activation. Design: A randomized, double-blinded, placebo-controlled crossover study was conducted in 90 healthy human subjects selected for normal platelet function. Changes from baseline hemostatic function were measured 3 h after consumption of extract-enriched or control supplements. Results: Significant reductions in ex vivo platelet aggregation induced by ADP and collagen were observed 3 h after supplementation with doses of tomato extract equivalent to 6 (6TE) and 2 (2TE) tomatoes <---------> No significant effects were observed for control supplements. A dose response to tomato extract was found at low levels of platelet stimulation. Inhibition of platelet function was greatest in a subgroup with the highest plasma homocysteine (P < 0.05) and C-reactive protein concentrations (P < 0.001). Conclusion: As a functional food or dietary supplement, tomato extract may have a role in primary prevention of cardiovascular disease by reducing platelet activation, which could contribute to a reduction in thrombotic events.