BACKGROUND: Although tube feeding modes have been shown to influence psychological status, the specific mechanism of action and differences between intermittent oro-esophageal tube feeding (IOE) and nasogastric tube feeding (NGT) have yet to be uncovered. This study explored the effect of IOE versus NGT on anxiety in patients with dysphagia after ischemic stroke. METHODS: This longitudinal observational study included patients with dysphagia after ischemic stroke who were treated in the Department of Rehabilitation Medicine between February 2022 and June 2024. Questionnaires, scales, and medical records were used to collect data regarding anxiety symptoms, basic information, treatment details, and self-perception on the 1st and 10th day of hospitalization. Propensity Score Matching (PSM) was used to balance potential confounding factors and analyze the association between IOE versus NGT and anxiety symptoms. Path analysis was conducted to explore the specific mechanisms of action. RESULTS: Totally, 2459 participants (55.51% IOE users) were recruited. The IOE users had significantly lower moderate-to-severe anxiety rates than the NGT users (25.88% and 44.42%, CONCLUSIONS: Compared to NGT, IOE can alleviate anxiety symptoms in patients with dysphagia after ischemic stroke who were treated in the Department of Rehabilitation Medicine. The relationship between tube feeding modes and anxiety symptoms was mediated by the self-perception of comfort, reflux, dietary schedule, social activity, self-esteem, and daily exercise.