Background: Patients with difficult weaning who undergo mechanical ventilation are more likely to be at risk of reintubation and the sequential use of oxygen therapy after extubation is a concern for clinicians.Therefore, the aim of the present study was to compare the effects of transnasal high-flow nasal cannula (HFNC) oxygen therapy and non-invasive positive-pressure ventilation (NIV) on respiratory mechanics in patients with difficult weaning.Methods: The present study was a single-center, retrospective, observational study. Twenty-nine patients with difficult weaning off invasive mechanical ventilation from the Department of Critical Care Medicine, The