We describe a case of an 81-year-old man with acute ST-elevation myocardial infarction (STEMI), who received a loading dose of clopidogrel (300 mg) and aspirin (ASA) (300 mg) prior to primary coronary intervention of critical left anterior descending coronary artery stenosis. Three days later he developed recurrent acute STEMI due to the in-stent thrombosis and a second stent implantation was performed. The dose of clopidogrel (75 mg) remained unchanged, while the dose of ASA was increased from 75 mg to 150 mg. Three days later the patient had an other STEMI due to the in-stent thrombosis and additional stent implantation with IIb/IIIa blocker was performed. Clopidogrel resistance was suspected. Therefore, clopidogrel was replaced by ticlopidine, the dose of ASA was increased and low-molecular heparin was administered. Since then, the patient has been clinically stable. Our case indicates the existence of a subgroup of patients with combined clopidogrel and ASA resistance.