AimAcute respiratory distress syndrome is the primary clinical problem that requires follow-up at the intensive care units. High Flow Nasal Cannula Oxygen Therapy has become an increasingly popular method by reducing the need for intubation but determining which patient will benefit from High Flow Nasal Cannula Oxygen Therapy is an important issue. Methods Seventy patients who followed up with acute respiratory distress syndrome related COVID-19 treated with High Flow Nasal Cannula Oxygen Systems as initial treatment at the intensive care units were retrospectively review. The primary endpoint of this study is to identify factors correlating with failure (mortality and invasive mechanical ventilator requirement) of High Flow Nasal Cannula Oxygen Therapy in the treatment of COVID-19-related severe ARDS. The secondary aim of this study is to determine the ROX index measured at the 12th hour, which will indicate the need for intubation in critically ill patients followed up with HFNC.Results Advanced age, male gender, and low ROX index were independent variables affecting High Flow Nasal Cannula Oxygen Therapy failure. While mortality was lowest in patients who completed the process with High Flow Nasal Cannula Oxygen Therapy treatment, patients who were intubated early (12-24h) had lower mortality than those who were intubated later (>24h) (Mortality rates were %4,3 ,%65,6 ,%93,3 respectively). The cut-off value for ROX index, which will indicate the need for intubation, was found to be 2.84. ConclusionHigh Flow Nasal Cannula Oxygen Therapy can be an effective treatment method in the follow-up of patients with COVID-19-related severe respiratory failure. Despite this, the requirement for intubation develops in two third of the patients. Early intubation reduces mortality in patients who fail High Flow Nasal Cannula Oxygen Therapy, and the easily calculated ROX index is a useful parameter to determine the need for intubation.