Objective To investigate the main influencing factors of cognitive dysfunction( CD) after acute ischemic stroke( AIS). Methods A total of 160 patients with AIS in Wuxi Branch of Zhongda Hospital Affiliated to Southeast University from January 2015 to January 2018 were selected. The patients were followed up for 90 days. The cognitive function of all patients was evaluated. Logistic regression analysis were applied to analyze the effects of AIS condition, vascular risk factors, serum biochemical indicators, lesion location and other clinical data on the occurrence of CD. Results In this study, 35.0%( 56/160) of 160 AIS patients developed cognitive impairment 90 days later. Increased age, less than 12 years of education, history of alcohol abuse, anemia and dyskinesia all lead to increased incidence of cognitive dysfunction( P< 0.05). Univariate analysis showed that the level of education, alcohol consumption, age, dyskinesia, hypersensitive C-reactive protein( hs-CRP), homocysteine( Hcy), occipital lobe( left), temporal lobe( left), dorsal thalamus, posterior thalamus and frontal lobe( left) were associated with the occurrence of CD in AIS patients 90 days after diagnosis. Multivariate regression analysis showed that education level, age alcohol consumption, dyskinesia, hs-CRP, Hcy, occipital lobe( left), dorsal thalamus and frontal lobe( left) were the risk factors for CD in AIS patients 90 days after diagnosis. Conclusions Understanding the basic information of AIS patients, the location of the lesion and the level of Hcy and hs-CRP in the body, and taking corresponding measures are of great significance to reduce the occurrence of cognitive impairment.