Objective To explore the effects of personalized antiplatelet therapy on the 90⁃day prognosis and safety in acute ischemic stroke（AIS）. Methods Participants were recruited in 14 hospitals. The study group received personalizedantiplatelet therapy，while the control group received conventional medications based on the clinical guideline.The rate of recurrence，mRS scores and bleeding events were recorded on day 90 and then com⁃ pared between the two groups. Results 1472 patients were recruited. In the study group，the patients with clopido⁃ grel resistance accounted for 61% and those with aspirin resistance was 9.4%. The rate of recurrence was 4.1% in the study group and 4.5% in the control group（P = 0.75）. The incidence of poor prognosis was 17.7% in the study group but 23.6% in the control group（P = 0.007）. The rate of bleeding events was 2.4% in the study group and 2.8% in the control group（P = 0.67）. Conclusions Personalized antiplatelet therapy can improve the short⁃term prognosis in patients with AIS and has no marked impacts on its safety. It provides evidence⁃based supports for clin⁃ ical precision medications.