Key PointsQuestionDoesCYP2C19loss-of-function metabolizer status, which blunts metabolism of clopidogrel to its active form, modify the degree of benefit of ticagrelor-aspirin or clopidogrel-aspirin for patients with minor stroke or transient ischemic attack?FindingsIn this prespecified subgroup analysis of the CHANCE-2 trial, new stroke occurred less often with ticagrelor-aspirin vs clopidogrel-aspirin, irrespective of metabolizer status: 6.0% vs 7.6%, respectively, among patients with intermediate metabolizer status and 5.7% vs 7.5%, respectively, among poor metabolizers. No difference was found in treatment effect between poor and intermediateCYP2C19metabolizers.MeaningThese findings suggest that it may be advisable to consider using ticagrelor-aspirin not only for poor metabolizers but also intermediate metabolizers for patients with transient ischemic attack or minor stroke, although caution should be taken when using ticagrelor added to aspirin due to the risk of any bleeding, particularly mild bleeding.