OBJECTIVE: To report a patient who experienced severe, reversible thrombocytopenia after receiving eptifibatide for acute coronary syndrome. CASE SUMMARY: A 61-year-old white man with a past medical history of coronary artery disease, peripheral vascular disease, insulin-dependent diabetes, hypertension, and dyslipidemia was treated with eptifibatide as an adjunct to standard antiischemic therapy for acute coronary syndrome. On administration of eptifibatide, the patient experienced chills accompanied by sharp pains that radiated throughout his body. The infusion was immediately stopped and the symptoms resolved. A platelet count obtained 11 hours later showed a decrease from a baseline of 230 to 3 × 103/mm3 (normal 160–360). Multiple platelet analyses confirmed profound thrombocytopenia. Over the course of the hospitalization, the patient's platelet count returned to normal; he experienced no other adverse hematologic sequelae. DISCUSSION: All of the glycoprotein IIb/IIIa receptor antagonists are associated with thrombocytopenia. However, the risk of thrombocytopenia has been observed to be less with eptifibatide. Because of the temporal relationship between eptifibatide administration and the patient's symptoms and laboratory analysis, we believe that the thrombocytopenia was the result of an adverse reaction. CONCLUSIONS: The temporal relationship to administration and the resolution of the adverse reaction on discontinuation of the drug support the likelihood that the severe, reversible thrombocytopenia was associated with eptifibatide.