Introduction. To date, information of the use of high-flow oxygen therapy (HFOT) in patients with tracheostomy cannulas is limited. The use of HFOT in this group of patients at the ventilator weaning may improve outcomes.Objective. Improving results of treatment of patients with tracheostomy cannulas with hypoxemic ARF of various origin through the use of HFOT at the ventilator weaning after prolonged mechanical ventilation (MV).Materials and methods. The prospective open cohort study included 50 patients aged 45 (from 37 to 57) years, the duration of invasive mechanical ventilation was 8.68 ± 3.83 days. Patients were randomized into two groups: in group A, weaning from the respirator was performed through a combination of traditional low-flow oxygen therapy (LFO) and assisted modes of MV; in group B – through a combination of HFOT and assisted modes of MV. The groups compared gas exchange rates, the duration of weaning from the respirator, the incidence of complications (pulmonary and extrapulmonary), the duration of treatment, mortality in the ICU and in the hospital. In all patients, the most significant predictors of in-hospital mortality were analyzed.Results. The use of HFOT in patients in group B revealed significant benefits in terms of the studied parameters in the early and late stages of the study. Mortality in the groups did not differ. The most significant risk factors for in-hospital mortality were cannulation after transfer from the OR (OR = 9,667; 95% CI: 2.414–38,713; p = 0,001).Conclusions. The use of HFOT in patients with tracheostomy cannulas is more clinically effective than COT. Risk factors assessment in every patient will allow optimal use HFOT.