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Goal: Significant proportions of stroke/transient ischemic attack events occur in patients taking daily aspirin. We studied the comparative effectiveness of Food and Drug Administration approved antiplatelet agents (aspirin, clopidogrel, and aspirin-dipyridamole combination) in prevention of recurrent vascular events in stroke/transient ischemic attack patients on aspirin.Materials and Methods: Consecutive patients having stroke or transient ischemic attack were screened and enrolled into this registry. Patients on long-term dual antiplatelet therapy or oral anticoagulants were excluded. Patient’s etiological stroke subtype, medication history, medication compliance, and Aspirin Platelet Function Test were assessed at baseline. Changes in antiplatelet regimen and statin therapy were also recorded. Follow up 6 and 12-month phone visits were conducted to assess primary outcomes of major adverse cardiovascular events that included a composite of death, myocardial infarction and stroke or transient ischemic attack.Result: One-hundred-eighty subjects (mean age ± SD= 68 ± 12 years, 59% male, 51% white, 49% African-American) were enrolled over 24-months. Majority (64%) had ischemic stroke (NIHSS: 0-21) and remaining (36%) had transient ischemic attack (ABCD2: 2-7). Within 12-months of the index cerebrovascular event, 3 (5.9%) participants on clopidogrel, 21 (18.8%) participants on aspirin and 7 (41.2%) participants on aspirin-dipyridamole combination had a composite vascular event (Log rank p=0.0011).Conclusion: This study shows a significant difference in major adverse cardiovascular event within 12 months of stroke/ transient ischemic attack on Aspirin, with effectiveness recorded in the order: clopidogrel>aspirin> aspirin-dipyridamole combination. A larger randomized pragmatic trial may help ascertain this finding and clarify if specific stroke subtypes benefit from specific antiplatelet agents.