Objectives To explore the efficacy of humidified and heated high flow oxygen therapy for the critically ill patients in intensive care unit (ICU) after extubation. Methods From January 2014 to December 2016, 487 patients were enrolled. Patients were allocated to two treatment groups randomly, which were humidified and heated high flow oxygen therapy group (236 patients, HFM group, aged 55.3±21.1 years old) and routine oxygen therapy group (251 patients, TO group, aged 58.4±19.3 years old). Blood oxygen saturation, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), fraction of inspired oxygen (FiO2), respiratory frequency, incidence rate of reintubation, ventilator-free days, ICU length of stay, and hospital stay were assessed and compared between the HFM group and the TO group. Results The hospital stay was similar in two groups. There were more ventilator-free days in the HFM group (P<0.05), fewer patients required reintubation (4.2%vs. 10.4%, P<0.05) and less ICU length of stay [(10.5±6.1) dvs. (14.3±8.5) d, P<0.05]. PaO2/FiO2 of the HFM group were better than the TO group after extubation at 2 h, 4 h, 8 h, 24 h, and 48 h (P<0.05). There were no statistically significant differences in respiratory frequency and PaCO2. Conclusions Humidified and heated high flow oxygen therapy can supply a better oxygenation for patients after extubation in ICU. It could be a common therapy in ICU for the critically patients after extubation.