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Abstract Background We determined the clinical presentation and outcomes of the Omicron variant of severe acute respiratory syndrome coronavirus 2 infection in hemodialysis patients and identified the risk factors for severe coronavirus disease (COVID-19) and mortality in the context of high vaccination coverage. Methods This was a retrospective cohort study involving hemodialysis patients who were vaccinated against COVID-19 during March–September 2022, when the Omicron variant was predominant, and the COVID-19 vaccination rate was high. The proportion of people with severe COVID-19 or mortality was evaluated using univariate logistic regression. Results Eighty-three (78.3%) patients had asymptomatic/mild symptoms, 10 (9.4%) had moderate symptoms, and 13 (12.3%) had severe symptoms. Six (5.7%) patients required intensive care admission, two (1.9%) required mechanical ventilation, and one (0.9%) was kept on high-flow nasal cannula. Of the five (4.7%) mortality cases, one was directly attributed to COVID-19 and four to pre-existing comorbidities. Risk factors for both severe COVID-19 and mortality were advanced age; number of comorbidities; cardiovascular diseases; increased levels of aspartate transaminase, lactate dehydrogenase, blood urea nitrogen/creatinine ratio, brain natriuretic peptide, and red cell distribution; and decreased levels of hematocrit and albumin. Moreover, the number of COVID-19 vaccinations wasa protective factor against both severe disease and mortality. Conclusions Clinical features of hemodialysis patients during the Omicron surge with high COVID-19 vaccination coverage were significant for low mortality. The risk features for severe COVID-19 or mortality were similar to those in the pre-Omicron period in the context of low vaccination coverage.