Objective. To assess efficacy and safety of methylprednisolone pulse therapy in patients with COVID-19. Materials and Methods. A retrospective analysis of 57 patients with moderate and severe novel coronavirus infection (COVID-19) receiving methylprednisolone pulse therapy (500 mg/day IV for 2–3 consecutive days) was performed. Pre- and post-therapy examination of the patients included clinical (severity and duration of fever, gas exchange parameters), imaging (computed tomography) and laboratory tests (including C-reactive protein, procalcitonin, D-dimer). Results. Methylprednisolone pulse therapy resulted in improved gas exchange (the mean duration of SpO2 recovery was 3.9 ± 0.25 days), body temperature normalization (the mean time to defervescence was 2.1 ± 0.2 days), significant decrease in inflammatory marker levels (CRP, D-dimer). No patients required an enhancement of respiratory support (transfer to ICU). Methylprednisolone pulse therapy was well-tolerated and did not cause bacterial complications. Conclusions. Methylprednisolone pulse therapy in patients with COVID-19 was shown to decrease activity of systemic inflammatory response, severity of coagulation disorders and contribute to recovery of gas exchange lung function. Given the high efficacy and low cost of methylprednisolone pulse therapy, it could be one of the promising approaches to the management of patients with moderate and severe COVID-19. Further studies are needed to determine prognostic criteria of progression and optimal time for initiation of corticosteroid therapy.