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Background: Although dual antiplatelet treatment with aspirin and clopidogrel is widely used in stroke patients due to large artery atherosclerosis (LAA), there are limited data to justify this.Methods: We used a multicenter, prospective stroke registry database (CRCS-K) to analyze acute ischemic stroke patients due to LAA who were treated with aspirin alone or combination of aspirin and clopidogrel from May, 2008 to May 2015. Results were analyzed by intention-to-treat (ITT), as-treated (AT), and per-protocol (PP) method. Primary endpoint was the 1-year composite outcome of stroke recurrence, myocardial infarction (MI), and all-cause death. To balance the differences between groups, a frailty model with inverse probability of treatment weighting was used.Results: A total of 5,934 patients due to LAA were treated either aspirin alone (n=3,031, 51%) or combination of aspirin and clopidogrel (n=2,903, 49%). Primary outcome was 14% (n=410) in aspirin alone group and 12% (n=353) in aspirin plus clopidogrel group. In ITT analysis, compared to aspirin alone, aspirin plus clopidogrel did not decrease the hazards of primary outcome (adjusted hazards ratio, 0.86; 95% confidence intervals, 0.74-1.01; p=0.06), but decreased all-cause mortality significantly (0.80; 0.66-0.98; p=0.03). Stroke recurrence and a composite of stroke recurrence, MI, and vascular death were not reduced by aspirin plus clopidogrel. Results of AT and PP analyses are shown in the table below.Conclusion: Addition of clopidogrel to aspirin may decrease all-cause death and perhaps the composite of stroke recurrence, MI and all-cause death in patients with large artery atherosclerotic stroke.