© 2021 John Wiley & Sons LtdBackground: Positioning of the patient is a common strategy to increase oxygenation in the management of acute respiratory distress syndrome. The aim of this study is to demonstrate the effects of our positioning approach on disease outcomes in COVID-19 patients with respiratory failure, by comparing patients compliant to positioning and not. Methods: COVID-19 patients who were admitted to our internal medicine inpatient clinic and developed hypoxaemia and underwent positioning during hospital stay were retrospectively investigated for compliance to positioning. Rates of mortality, intensive care unit admission, intubation, initiation of anti-inflammatory treatment and length of hospital stay were compared between patients with and without compliance to positioning. Results: A total of 144 patients were enrolled in this study (97 compliant with positioning, 47 incompliant with positioning). Rates of ICU admission (7.2% vs 25.5%, p <.001), anti-inflammatory treatment initiation (68% vs 97.9%, p <.001) and length of hospital stay (5 (2-16) days vs 12 (3-20) days, p <.001) were significantly reduced in patients compliant with positioning. Conclusion: Prone or other positioning should be considered in patients with noninvasive oxygen support for the potential to reduce rates of intensive care unit admissions, airway interventions, anti-inflammatory treatment initiation and mortality.