Objective To compare the clinical characteristics, inflammatory indexes and coagulation function of patients with acute ischemic stroke complicated with coronavirus disease 2019 (COVID-19) and those without COVID-19, and to explore the risk factors of acute ischemic stroke after COVID-19. Methods A single-center retrospective study was conducted in 187 patients with acute ischemic stroke who were treated in our hospital from Nov. 5, 2022 to Feb. 5, 2023 and were tested for COVID-19, including 75 patients with COVID-19 (COVID-19 group) and 112 patients without COVID-19 (non-COVID-19 group). The general clinical data, inflammation and coagulation function indexes (neutrophil-lymphocyte ratio[NLR], D-dimer, and fibrinogen[FIB]) of the 2 groups were analyzed. Multivariate logistic regression was used to analyze the independent risk factors of acute ischemic stroke after COVID-19 infection. Results NLR (3.62[2.31, 6.71] vs 2.64[1.87, 5.04], P=0.014), D-dimer (0.70[0.32, 2.27] mg/L vs 0.37[0.27, 0.76] mg/L, P=0.001) and FIB (4.21[3.26, 5.17] g/L vs 3.25[2.77, 3.87] g/L, P<0.001) of COVID-19 group were markedly higher than those of non-COVID-19 group, and lymphocyte count (1.40[1.03, 1.71]×10⁹/L vs 1.61[1.09, 2.21]×10⁹/L, P<0.05) was lower than that of non-COVID-19 group. Multivariate logistic regression analysis showed that the previous stroke history (odds ratio[OR]=5.430, 95% confidence interval[CI]1.538-19.175, P=0.009), D-dimer (OR=1.425, 95% CI 1.104-1.840, P=0.007) and FIB (OR=2.405, 95% CI 1.683-3.437, P<0.001) were independent risk factors for acute ischemic stroke after COVID-19. Conclusion Serum biomarkers of inflammation and coagulation function (NLR, D-dimer, and FIB) are increasesd in patients with acute ischemic stroke after COVID-19, and the incidence of ischemic stroke after COVID-19 is related to hypercoagulability.