BACKGROUND: Clopidogrel inhibits platelet P2Y12 adenosine diphosphate (ADP) receptors and has been widely used in patients with ischemic stroke. However, a considerable number of patients suffer from cerebrovascular events despite the use of clopidogrel. The rapid platelet function assay (RPFA) has been used for monitoring the antiplatelet effects on the P2Y12 ADP receptor. This study was performed to measure the platelet response to clopidogrel using RPFA in patients with ischemic stroke, and to identify the clinical factor related with clopidogrel resistance. METHODS: A total of 86 patients taking clopidogrel (75 mg/day) were enrolled. Demographic data, vascular risk factors, the presence of obesity and metabolic syndrome, drug history, hemoglobin, platelet counts, and stroke subtypes were recorded. RPFA presented the results as P2Y12 Reaction Units (PRU), base PRU (BASE), and Inhibition (%). Inhibition was calculated as (1-PRU/BASE)x100. The patients showing ineffective aggregation- inhibition (percentage of Inhibition < 20) on RPFA were defined as non-responders to clopidogrel. RESULTS: The response of platelet aggregation-inhibition to clopidogrel showed a variable distribution with mean and standard deviation of 32.2+/-22.3%. Twenty four (27.9%) patients showed the inhibition below 20%. There was no difference between responders and non-responders regarding the clinical factors above. We found no influence of co-medication with the statins on platelet response to clopidogrel. CONCLUSIONS: There is a patient variability in response to clopidogrel and a considerable portion of stroke patients have clopidogrel resistance on the platelet function test. The clinical usefulness of routine platelet function test requires further validation.