The article presents a comparative retrospective analysis of clinical, laboratory data and outcomes in 39 patients with severe COVID-19 complicated by acute respiratory distress syndrome, who received high-flow oxygen therapy. Of which, 19 patients additionally received 75 mg of inhaled surfactant BL twice daily for 5 days using a nebulizer. As a result, mortality rate in the group of patients receiving surfactant was 10.5%, while in the standard therapy group — 50%; the number of patients transferred to the mechanical ventilation was 21% and 70%, respectively. As the patients receiving the surfactant were injected with COVID-19 hyperimmune convalescent plasma and monoclonal antibodies to interleukin-6 receptors more often than those from the control group, we recalculated the results regardless of these patients. However, a significant difference between the mechanical ventilation rate (2.5 times less often in the surfactant group) and mortality rate (3.5 times less in the surfactant group) was observed. The duration of hospitalization and stay at the intensive care unit was not significantly different between patients with and without surfactant treatment. Inhalation therapy with surfactant BL was well tolerated even by patients with chronic obstructive pulmonary disease. In no case did therapy have to be stopped due to side effects, the most common of which was coughing during inhalation. This retrospective analysis shows that the prescription of an inhaled surfactant prior to transferring patients to mechanical ventilation can prevent the progression of respiratory failure, put down mechanical ventilation, and improve survival. © 2020, Remedium Group Ltd. All rights reserved.