Background and Purpose: The optimal strategy for the treatment of symptomatic intracranial atherosclerotic stenosis has not been established. We compared the efficacy of 2 antiplatelet drug combinations aspirin plus cilostazol compared with aspirin plus clopidogrel for the progression of ICAS, which is known to be associated with clinical stroke recurrence. Methods: In this investigator-initiated double-blind trial, 457 patients with acute symptomatic middle cerebral artery or basilar artery M1 segment stenosis were randomly assigned to either the cilostazol or clopidogrel group. After 7 months of treatment, patients were followed up with MR angiography and MRI. the primary endpoint was progression of ICAS compared with stenosis at baseline MR angiography. Secondary endpoints included new ischemic damage on MRI, the occurrence of composite cardiovascular events, and major bleeding complications. Results: Cardiovascular events occurred in 15 of 232 patients in the cilostazol group and in 10 of 225 patients in the clopidogrel group. Relative to clopidogrel, cilostazol did not reduce the progression of symptomatic ICAS, although favorable changes in serum lipoproteins were observed in the cilostazol group. There were no significant differences in new ischemic damage or major bleeding complications between the two groups. CONCLUSIONS: This trial failed to show a significant difference in the prevention of progression of ICAS and new ischemic damage in patients with symptomatic ICAS with the combination of 2 antiplatelet agents.