Background. During the pandemic of coronavirus infection (COVID-19) caused by a virus SARS-CoV-2 there has been significant variability in symptoms of the disease over time, severity of the course and in particular hospital mortality. Several SARS-CoV-2 variants have been identified such as Alpha, Delta, Omicron and others. Aim. To investigate the hospital mortality in patients with different strain variants during the period from April 2020 to April 2022. All included patients had moderate to severe COVID-19-associated pneumonia requiring hospitalization. Materials and methods. In this retrospective, conclusive, non-randomized, non-controlled study 4854 clinical records of hospitalized patients with Alpha (n=2400, April – December 2020), Delta (n=1722, 2021) and Omicron (n=627, January – April 2022) variants were investigated. Results. Hospital mortality is 6% in Alpha variant patients (6%), 5.7% in Delta and significantly lower in Omicron (1.5%; p0,001). Cardiovascular disease (arterial hypertension, coronary heart disease, chronic heart failure), diabetes mellitus and chronic kidney disease were risk factors for death in Alpha and Delta, but not in Omicron. There was also a significant decrease in the duration of hospitalization with strains Delta [7 days (5; 9)] and Omicron [7 (5; 11)] compared with Alpha [11 (9; 13); p0,001], and differences in factors the risk of mortality between the tested COVID variants. Conclusion. Thus, differences in mortality and risk factors for death between COVID-19 variants could be shown in our cohort.