Abstract: Objective To study the effects of different oxygen inhalation methods on reintubation rate and oxygenation index of ICU patients after weaning. Methods A total of 122 ICU patients with endotracheal intubation who underwent mechanical ventilation were selected as research objects. According to the random number table method, they were randomly divided into study group and control group, with 61 cases in each group. The control group was treated by routine oxygen inhalation after weaning, while the study group was treated by transnasal high-flow oxygen inhalation, and other care and treatments were the same in both groups. The changes in oxygenation index and re-intubation rate of the two groups were observed and compared. Results After treatment, the intubation rate of the study group was significantly lower than that of the control group(6.6% vs. 19.7%, P<0.05). The respiratory frequency and partial carbon dioxide pressure of the study group at 1, 8, and 24 h after treatment were significantly lower than those of the control group, and the arterial oxygen partial pressure and oxygenation index were significantly higher than those of the control group, the differences between the two groups were statistically significant(P<0.05). Conclusion Transnasal high-flow oxygen inhalation after weaning for ICU patients can effectively reduce re-intubation rate and increase the oxygenation index, which is a new and an effective breathing support mode.