Background: COVID-19 is associated with clinical features that closely resemble acute respiratory distress syndrome and causes hypoxic respiratory failure requiring ventilator support. The primary purpose of this study is to investigate the effects of high-dose methylprednisolone on the respiratory condition of COVID-19 patients on the intensive care unit (ICU) in the absence of early treatment with hydrocortisone Methods: This retrospective observational study reports on all patients who were hospitalised with COVID-19 and received mechanical ventilation while on the ICU in Rijnstate Hospital. These patients received intravenous methylprednisolone following the ‘Meduri protocol’. The primary outcome was defined as improvement of the respiratory conditions expressed by P/F ratio and PEEP. Results: Seventeen of the 42 COVID-19 patients admitted to our ICU received methylprednisolone, initiated at day 13 (median). The mean length of ICU stay of these patients was 34 days. The average P/F ratio improved significantly from 14.2 kPa (107 mmHg) to 17.9 kPa (135 mmHg) after one week of treatment and from 17.9 kPa to 20.8 kPa (158 mmHg) after two weeks of treatment. This also applies to the positive endexpiratory pressure (PEEP), which decreased significantly to 9 cmH2O and 7 cmH2O after one and two weeks of treatment, respectively, compared with 10 cmH2O before start of the protocol. In our population the 28-day mortality was 18% versus an overall in-hospital mortality of 29% in patients with COVID-19. Conclusion: In patients with COVID-19 who received mechanical ventilation on the ICU, the use of high-dose methylprednisolone seemed to provide a significant improvement in both oxygenation and ventilation. © 2021, Netherlands Society of Intensive Care. All rights reserved.