Previous studies in our laboratory have shown that antiplatelet agents, aspirin and ticlopidine, in clinically relevant concentrations influence the development and treatment of experimental endocarditis. To study the influence of combination antiplatelet treatment on the development of aortic vegetations, infected animals received either aspirin alone, ticlopidine alone, aspirin plus ticlopidine or no antiplatelet therapy. The combination antiplatelet treated group had a statistically significant (P = 0.043) reduction of the vegetative weight as compared with the untreated controls. While both the single antiplatelet agent groups showed a reduction in the size of the vegetation, neither achieved statistical significance. None of the treatment groups significantly altered the bacterial density relative to untreated controls. These findings reveal that the combination of aspirin and ticlopidine, two potent inhibitors of platelet aggregation with different mechanisms of action, act synergistically to optimally reduce the weight of aortic valve vegetations.