The Global Trigger Tool is a reliable method for detecting adverse events, demonstrating positive predictive value and significant sensitivity among patients with COVID-19. The objective of this study was to develop and apply an adapted Global Trigger Tool to identify potential adverse events among hospitalized patients with moderate to severe COVID-19. Materials and methods . The study included a literature review, analysis of spontaneous reports n=873 in the national database of the Russian Federation for the COVID-19 indication for the period 2020–2022, and application of the trigger tool in a single-center retrospective study n=329. Statistical processing was performed by the method of disproportionality with the determination of the odds ratio of reporting. The symptom-syndrome method based on parameterization of interaction effects using Zhegalkin polynomials was used to identify significant effects of drug associations; Fisher’s exact test was used to select the most significant associations for occurrence. Results. Among the triggers with a frequency of 10 or higher in terms of mortality rate (≥80%), the leading ones were: pulmonary edema, hypotension, and respiratory failure, which is consistent with the COVID-19 clinical course of the disease. A disproportionately high incidence of respiratory failure was associated with favipiravir use. Leukocytosis associated with tofacitinib use and drug-induced liver damage associated with tocilizumab use. Conclusions. The identified potential adverse events and their associated mortality risks among patients with moderate to severe COVID-19 allow for compliance with current clinical guidelines for the management of patients with COVID-19.