Objective To investigate the embolism causes, and the imaging and clinical characteristics of patients with embolic stroke of undetermined source (ESUS), and analyze the differences of acute ischemic stroke with large vessel occlusion (AIS-LVO) caused by large artery atherosclerosis and cardioembolism.Methods A total of 127 patients, who were admitted to Department of Emergency of our hospital from Jan. 2018 to Dec. 2019 with anterior circulation AIS-LVO suggested by multimodal computed tomography (CT) and underwent endovascular treatment, were retrospectively included. Twenty-nine patients had ESUS, 40 had large artery atherosclerosis and 58 had cardioembolism. The scores of National Institutes of Health stroke scale (NIHSS) and Glasgow coma scale (GCS) on admission, the volumes of infarction core and ischemic penumbra, Alberta Stroke Program early computed tomography score (ASPECTS) and hypoperfusion intensity ratio (HIR) were compared among the 3 groups. Multivariate logistic regression model was used to evaluate the differential value of imaging features for ESUS and large artery atherosclerosis.Results There were significant differences in the NIHSS and GCS scores on admission, infarction core volume, ASPECTS and HIR between the ESUS, large artery atherosclerosis and cardioembolism groups (all P < 0.05). The results of multiple comparison showed that the GCS score on admission in the ESUS group was significantly lower than that in the large artery atherosclerosis group, and the infarction core volume and HIR were significantly higher than those in the large artery atherosclerosis group (all P < 0.05); there were significant differences in the NIHSS and GCS scores on admission, infarction core volume, ASPECTS and HIR between the large artery atherosclerosis group and cardioembolism group (all P < 0.05); while there were no significant differences in the NIHSS and GCS scores on admission, infarction core volume, ischemic penumbra volume, ASPECTS or HIR between the ESUS group and cardioembolism group (all P > 0.05). Multivariate logistic regression analysis showed that HIR had independent predictive value for ESUS in patients with anterior circulation AIS-LVO (odds ratio=9.757 0, 95% confidence interval 1.203 4-79.107 2, P=0.03).Conclusion Compared with the AIS-LVO caused by large artery atherosclerosis, the imaging characteristics of ESUS are more similar to those of AIS-LVO caused by cardioembolism, suggesting that most ESUS may be caused by cardioembolism. HIR has guiding value for the judgment of the etiology of anterior circulation AIS-LVO.