Background <p>The prognostic period and factors associated with coronavirus disease (COVID-19) in patients on hemodialysis (HD) with high mortality due to COVID-19 are important for the treatment and management of patients on HD after COVID-19 infection. In previous studies, the observation period of prognosis in patients on HD with COVID-19 was 1 year or less, and few reports have examined long-term prognoses of over 3 years or more. Moreover, few studies have examined patient prognosis based on clearly defined severity rather than on hospitalization. In this prospective observational study, we investigated the relationship between the severity of COVID-19 at disease onset and the long-term prognosis of COVID-19-infected patients on HD.</p> Methods <p>In total, 373 patients on HD diagnosed with COVID-19 were included in this study. The follow-up period ranged from onset up to 3 years. Patient background, blood samples and chest computerized tomography scans were examined. Severity was classified into four categories based on peripheral oxygen saturation and clinical status. Three categories, namely moderate I, moderate II, and severe, were defined as the moderate or severe group, and one category, namely mild, was defined as the mild group.</p> Results <p>There were 255 patients in the mild stage, 70 in the moderate I stage, 45 in the moderate II stage, and three in the severe stage; therefore, 118 patients were in the moderate or severe group. The prognosis in the moderate or severe disease group was lower than that in the mild disease group, according to Kaplan–Meier curves. Moderate or severe disease, older age, and lower levels of albumin were risk factors for mortality according to the Cox proportional hazards model of multivariate analysis. Only eight of the 373 patients died from a direct cause of COVID-19 within 7 days after COVID-19 diagnosis.</p> Conclusions <p>Moderate or severe COVID-19 worsens the prognosis of patients on HD up to 3 years.</p>