Recently, great interest has focused on the phenomenon of aspirin resistance, which may be defined as clinical or laboratory resistance. Monitoring the antiplatelet effect appears to be relevant in the presence of clinical implications, but no data are available on the possible clinical implications of the failure of aspirin to inhibit tests of platelet function in the setting of acute coronary syndromes. This study evaluated the role of aspirin resistance in the occurrence of 1-year major adverse coronary events (MACEs) in patients with acute myocardial infarction (AMI) who have undergone percutaneous coronary intervention (PCI). We prospectively evaluated 146 patients (115 men and 31 women; median age 65 years, range 30 to 84) with AMI who underwent primary PCI. Exclusion criteria were the use of glycoprotein IIb/IIIa inhibitors, hematocrit <or=30%, and a platelet count <100,000/mm3. Platelet function analyzer-100 closure times by collagen-epinephrine were used for measuring platelet function in venous blood samples obtained 12 to 15 hours after revascularization. Patients were considered aspirin resistant in the presence of a collagen-epinephrine closure time of <203 seconds. After 1-year follow-up, MACEs were recorded in 44 of 146 patients (30.1%). A significantly higher percentage of patients with MACEs had aspirin resistance (39.1% vs 23.2%, p <0.05). A Kaplan-Meier survival curve showed that the overall risk of MACEs was significantly higher among patients with aspirin resistance (p = 0.02). A Cox regression analysis that adjusted for age, gender, traditional cardiovascular risk factors, systolic left ventricular function, number of stenosed coronary arteries, and previous AMI, PCI, or coronary artery bypass graft showed aspirin resistance to be a significant and independent risk factor for the future MACEs (hazard ratio 2.9, 95% confidence interval 1.1 to 9.2, p <0.05). In conclusion, our data demonstrate that aspirin resistance after PCI is a significant and independent predictor of MACEs in patients with AMI undergoing primary PCI.