A controlled, open-label trial evaluated the effectiveness of dexamethasone in hospitalized patients with Covid-19. The study randomly assigned 2104 patients to receive dexamethasone (6 mg daily for up to 10 days) and 4321 patients to receive usual care. The primary outcome was 28-day mortality, which was significantly lower in the dexamethasone group (22.9%) compared to the usual care group (25.7%) (rate ratio, 0.83; 95% CI, 0.75 to 0.93; P<0.001). The benefit of dexamethasone was most pronounced in patients receiving invasive mechanical ventilation (29.3% vs. 41.4%) and those receiving oxygen without invasive ventilation (23.3% vs. 26.2%), but not in those not receiving respiratory support (17.8% vs. 14.0%). The trial, funded by the Medical Research Council and National Institute for Health Research, found that dexamethasone reduced 28-day mortality in patients with Covid-19 who required respiratory support at randomization. The results were consistent with previous findings in patients with acute respiratory distress syndrome. The study highlights the importance of respiratory support in determining the effectiveness of dexamethasone. The trial was conducted rapidly, with results announced on June 16, 2020, and led to updated guidelines recommending dexamethasone for hospitalized patients with Covid-19. The study underscores the need for further research to understand the mechanisms of dexamethasone's effects in different patient populations.A controlled, open-label trial evaluated the effectiveness of dexamethasone in hospitalized patients with Covid-19. The study randomly assigned 2104 patients to receive dexamethasone (6 mg daily for up to 10 days) and 4321 patients to receive usual care. The primary outcome was 28-day mortality, which was significantly lower in the dexamethasone group (22.9%) compared to the usual care group (25.7%) (rate ratio, 0.83; 95% CI, 0.75 to 0.93; P<0.001). The benefit of dexamethasone was most pronounced in patients receiving invasive mechanical ventilation (29.3% vs. 41.4%) and those receiving oxygen without invasive ventilation (23.3% vs. 26.2%), but not in those not receiving respiratory support (17.8% vs. 14.0%). The trial, funded by the Medical Research Council and National Institute for Health Research, found that dexamethasone reduced 28-day mortality in patients with Covid-19 who required respiratory support at randomization. The results were consistent with previous findings in patients with acute respiratory distress syndrome. The study highlights the importance of respiratory support in determining the effectiveness of dexamethasone. The trial was conducted rapidly, with results announced on June 16, 2020, and led to updated guidelines recommending dexamethasone for hospitalized patients with Covid-19. The study underscores the need for further research to understand the mechanisms of dexamethasone's effects in different patient populations.