BackgroundAlthough almost a year has passed since the Coronavirus disease 2019 (COVID-19) outbreak and promising reports of vaccines have been presented, we still have a long way until these measures are available for all. Furthermore, unsolved issues remained to choose appropriate corticosteroids treatment for COVID-19. We conducted a study to assess the effectiveness of methylprednisolone treatment versus dexamethasone for hospitalized COVID-19 patients.MethodIn this prospective triple-blinded randomized controlled trial, we enrolled 86 hospitalized COVID-19 patients from August to November 2020, in Shiraz, Iran. Patients were randomly allocated into two groups to receive either methylprednisolone (2mg/kg/day) or dexamethasone (6mg/kg/day). Data was assessed based on a 9-point WHO ordinal scale extending from uninfected (point 0) to death (point 8).ResultsThere was no significant variation among the groups on the admission. However, the intervention group demonstrated significantly better clinical status compared to the control group at day 5 (4.02 vs. 5.21, P = 0.002) and day 10 (2.90 vs. 4.71, P = 0.001) of admission. There was also a significant difference in the overall mean score between the intervention group, and the control group, (3.909 vs. 4.873 respectively, P = 0.004). The mean length of hospital stay was 7.43 ± 3.64 and 10.52 ± 5.47 days in the intervention and control groups, respectively (P = 0.015). The need for a ventilator was significantly lower in the intervention group than in the control group (18.2% vs 38.1% P = 0.040).ConclusionIn the context of treating hospitalized hypoxic COVID-19 patients, methylprednisolone demonstrated better results compared to dexamethasone.Trial Registration:The trial was registered with IRCT.IR (08/04/2020-No. IRCT20200204046369N1).