A 62-year-old man with a history of coronary artery disease and coronary artery bypass graft, chronic heart failure, and peripheral vascular disease required percutaneous coronary intervention (PCI) after progression of shortness of breath and fatigue over 2 years. Four hours after the procedure, the patient developed hematemesis and was found to be thrombocytopenic. The thrombocytopenia was presumed to be due to the abciximab infusion the patient received during and shortly after the PCI. Further review of the patient's medical history revealed that a similar episode had occurred 11 years earlier. At that time, he was enrolled in a clinical trial comparing tirofiban and heparin in patients with unstable angina; he developed profound thrombocytopenia within 24 hours of randomization. After the study unblinding, investigators discovered that the patient received tirofiban, which was thought to be the cause of his thrombocytopenia. Both abciximab and tirofiban are glycoprotein IIb-IIIa inhibitors, and thrombocytopenia induced by this class of drugs is a serious and potentially life-threatening adverse reaction. The mechanism is not well understood but has been described as immune mediated with both ligand-mimetic agents (tirofiban and eptifibatide) and abciximab. Our patient's situation was unusual in that he developed thrombocytopenia from a ligand-mimetic agent and subsequently had a similar reaction to abciximab. To our knowledge, this case report is the first documentation of thrombocytopenia associated with both tirofiban and abciximab in a single patient, and suggests that care should be given in administering glycoprotein IIb-IIIa inhibitors of either type to patients with a history of thrombocytopenia due to one of these agents.