We report about a 72-year-old woman who was admitted to our hospital because of an acute ST-elevation myocardial infarction (STEMI). At admission, she received a loading dose of 300 mg Clopidogrel and 500 mg aspirin (ASA) prior to angioplasty with stenting of a 90% diameter stenosis of the proximal right coronary artery. After intervention, 75 mg Clopidogrel and 300 mg ASA OD were continued. Three days later, she developed a recurrent acute STEMI due to stent thrombosis and a second stent implantation was performed. The dose of Clopidogrel and ASA remained unchanged. Three days later, the patient suffered a third STEMI due to a restent thrombosis and additional stent implantation was performed. The dose of Clopidogrel and ASA was increased to 75 mg BD and 500 mg OD. Platelet function analysis and aggregation studies demonstrated dose-independent ASA resistance. ADP-induced aggregation showed a short-term platelet inhibition with subsequent rapid normalisation, thus suggesting Clopidogrel resistance. Therefore, the treatment was changed to coumadin and ASA 100 mg OD. Since then, the patient has been clinically stabile. Our case indicates for the first time the existence of a subgroup of patients with combined Clopidogrel and ASA resistance. We conclude that identification of these patients is required and alternative therapeutic options have to be considered.