In this prespecified subgroup analysis of the CHANCE-2 trial, we investigated outcomes among patients with TIA or minor ischemic stroke with ticagrelor-aspirin or clopidogrel-aspirin based on background CYP2C19 genotype and found that new stroke occurred less often with ticagrelor-aspirin vs clopidogrel-aspirin, irrespective of metabolizer status: 6.0% vs 7.6%, respectively, among intermediate metabolizers (a significant 22% relative risk reduction), and 5.7% vs 7.5%, respectively, among poor metabolizers (a nonsignificant 23% relative risk reduction). This evidence concerns the gene CYP2C19 and stroke disorder.