Abstract： Objective:To compare the effects of high-flow humidified oxygen therapy (HFHO) and T-tube weaning on weaning effect and the infection rate of ventilator-associated pneumonia (VAP) in patients with difficult weaning, so as to find a more reasonable weaning scheme.Methods:This was a cohort study.From January 2015 to August 2021, a total of 164 patients with difficult weaning who met the selection criteria admitted to the Department of Critical Care Medicine, 8th Medical Center of Chinese PLA General Hospital, with mechanical ventilation ≥24h, and who met the inclusion criteria of difficult weaning were selected non randomly, and they were divided into HFHO group (80 cases) and T-tube group (84 cases). The demographic data of the patients in the two groups, the success rate of weaning, the re-intubation rate within 7 days, the infection rate of VAP, and the airway humidification effect were all compared.Results:Before weaning, PaO 2 and oxygenation index of HFHO group were lower than those of T-tube group, which were 104(86.00, 137.50) mmHg vs 125(99.00, 155.80) mmHg, (311.9±39.4) vs (355.6±129.5) respectively ( Z=2.54, t=2.41, P<0.05). There was no significant difference in the weaning success rate between HFHO group and T-tube group, with 73.75%(59/80) vs 59.52%(50/84)( χ2=3.72, P=0.054). Among 94 patients with tracheal intubation, 40 patients chose HFHO weaning and 54 patients chose T-tube weaning, and the success rate of two weaning modes was analyzed again.The weaning success rate of tracheal intubation patients in the HFHO group was significantly higher than that of the T-tube group, 92.50%(37/40) vs 59.26% (32/54), ( χ2=13.01, P<0.01). The secondary intubation rate within 7 days of tracheal intubation patients in the HFHO group was lower than that of the T-tube group, 8.10% (3/37) vs 28.13% (9/32), ( χ2=4.79, P<0.05). Sputum viscosity (Ⅰ, Ⅱ, Ⅲ) in HFHO group was better than that in T-tube group, which were 26.25%(21/80), 53.75%(43/80), and 20.00%(16/80) vs 11.90%(10/84), 60.71%(51/84), and 27.38%(23/84); good rate of airway humidification in HFHO group was also better than that in T-tube group, with 63.75%(51/80) vs 40.48%(34/84). There was no significant difference in VAP infection rate between the two groups ( P>0.05). Conclusions:HFHO weaning mode is more suitable for patients with difficult weaning.