Antiplatelet therapy has been shown to reduce the size of aortic vegetations in a rabbit model of Staphylococcus aureus endocarditis. In addition, adjunctive aspirin improved the sterilization rate as compared with antibiotic treatment alone. To study the influence of ticlopidine, another potent inhibitor of platelet aggregation, infected animals received either vancomycin (Vm) alone or in combination with ticlopidine. When ticlopidine was given prior to and during antimicrobial therapy, a reduction in vegetation weight was observed. Ticlopidine administered with antimicrobial therapy, not only caused a reduction in vegetation weight, but also improved the rate of sterilization. This study provides additional data regarding the potential clinical role of antiplatelet agents in the treatment of endocarditis.