To investigate the effect of prior ischemic stroke on the outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19), and to describe the incidence, clinical features, and risk factors of acute ischemic stroke (AIS) following COVID-19.In this population-based retrospective study, we included all the hospitalized positive patients with COVID-19 at Wuhan City from December 29, 2019 to April 15, 2020. Clinical data were extracted from administrative datasets coordinated by the Wuhan Health Commission. The propensity score matching and multivariate logistic regression analyses were used to adjust the confounding factors.There are 36,358 patients in the final cohort, in which 1,160 (3.2%) had a prior stroke. After adjusting for available baseline characteristics, patients with prior stroke had a higher proportion of severe and critical illness and mortality. We found for the first time that the premorbid modified Rankin Scale (MRS) grouping (odds ratio [OR] = 1.796 [95% CI 1.334-2.435], p < 0.001) and older age (OR = 1.905 [95% CI 1.211-3.046], p = 0.006) imparted increased risk of death. AIS following COVID-19 occurred in 124 (0.34%) cases, and patients with prior stroke had a much higher incidence of AIS (3.4%). Logistic regression analyses confirmed an association between the severity of COVID-19 with the incidence of AIS. COVID-19 patients with AIS had a significantly higher mortality compared with COVID-19 patients without stroke and AIS patients without COVID-19.Coronavirus disease 2019 patients with prior stroke, especially those with the higher premorbid MRS or aged, have worse clinical outcomes. Furthermore, COVID-19 increases the incidence of AIS, and the incidence is positively associated with the severity of COVID-19.Copyright © 2022 Wang, Zhang, He, Qin, Liu, Liu, Tang, Li, Yang, Tang, Liang, Xu and Wang.