Platelet glycoprotein IIB/IIIA antagonists are potent inhibitors of platelet aggregation. Although the incidence of thrombocytopenia following their administration is relatively low, it can sometimes lead to fatal consequences. We report a case of a 57-year-old gentleman presenting with non-ST elevation myocardial infarction complicated with tirofiban-induced profound thrombocytopenia that developed within 12 hours of administration. Given the high risk of acute-onset thrombocytopenia following treatment with glycoprotein IIb/IIIa inhibitors, platelet count monitoring is highly encouraged at frequent intervals. This case highlights the importance of early detection and treatment of thrombocytopenia.