Epidemiological data have reported an inverse relationship between the consumption of tomatoes and tomato products and the risk of cardiovascular disease. However, the mechanism(s) by which tomatoes may reduce cardiovascular disease risk are not yet known. The present study sought to determine whether an aqueous tomato fraction (tomato extract) could inhibit platelet aggregation in vitro. Platelet-rich plasma was prepared from human blood and incubated in the presence or absence of tomato extract prior to stimulating the platelets with known agonists. Collagen-induced and adenosine diphosphate-induced platelet aggregation were significantly inhibited by the tomato extract (P<0.001), whereas no effect was observed on arachidonic acid-induced platelet aggregation. The inhibition of platelet aggregation by tomato extract was found to be dose dependent and increased with longer incubation times. Basal cAMP levels were not significantly different in the presence of the tomato extract as compared with control levels. Therefore, the mechanism by which the tomato extract inhibits platelet aggregation appears to be through inhibition of biochemical events in the phospholipase C pathway upstream of cyclooxygenase, rather than through increased cAMP levels. These results provide a potential mechanism by which tomatoes contribute to cardiovascular health.