Background: In patients with acute stroke and middle cerebral artery (MCA) stenosis, microembolic signals (MES) can predict further cerebral ischemia. Therefore, this study was designed to evaluate the prevalence of MES by transcranial Doppler (TCD) in patients with MCA stenosis under treatment of aspirin or clopidogrel.Methods: A randomized clinical trial was performed on 40 patients with acute ischemic stroke in MCA territory. They were randomly allocated in two groups that treated with aspirin (80 mg daily) or clopidogrel (75 mg daily). Clinical and diagnostic work up was included evaluation of cerebrovascular risk factors, echocardiography, carotid color Doppler and brain imaging. TCD was performed between day 3 and 7 after symptoms onset to detect MES. All high intensity transient signals (HITS) were saved and analyzed offline.Results: Carotid stenosis was found in 13 (65%) patients of aspirin group and 12 (60%) of clopidogrel group. Four (30.8%) of aspirin group and 5 (41.7) of clopidogrel group had stenosis between 10%-50%. One patient in each group had more than 50% stenosis and the remainder had less than 10%. There was no significant difference between two groups. MES was detected in 6 (30%) of patients treated with aspirin and 4 (20%) of those treated with clopidogrel. It showed no statistically significant differences (P-value=0.46).Conclusion: Our results indicate a similar effect of aspirin and clopidogrel on frequency of MES in patients with MCA territory ischemic stroke.