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Background: Coronavirus disease 2019 (COVID-19) infection in India demonstrated three peaks in India, with differences in presentation and outcome in all the three waves. The aim of the paper was to assess differences in the epidemiological, clinical features and outcomes of patients with COVID-19 presenting at a tertiary care hospital in the three waves at Jaipur, India. Methods: This was a retrospective study conducted at a tertiary care hospital at Jaipur, India. Demographic, clinical features and outcomes were compared of confirmed COVID-19 cases admitted during the first wave (16-7-2020 to 31-1-2021), second wave (16-3-2021 to 6-5-2021) and third wave (1-1-22 to 20-2-22) of the outbreak. Results: There were 1006 cases, 639 cases and 125 cases admitted during the three waves, respectively. The cases presenting in the second wave were significantly younger, with significantly higher prevalence of symptoms such as fever, cough, sore throat, nausea, vomiting, headache, muscle ache, loss of appetite and fatigue (P < 0.05). A significantly higher proportion of patients received Remdesivir in the second wave (P < 0.001). However, in the second wave, the use of low molecular weight heparin, plasma therapy, non-invasive and invasive ventilator were higher (P < 0.001). Co-morbid conditions were significantly higher in the admitted patients during the third wave (P < 0.05). Radiological scores were similar in second and third wave, significantly higher than the first wave. Lymphopenia and rise of inflammatory markers including C-reactive protein and interleukin-6 were more evident in the second wave (P < 0.001). The mean mortality, hospital stay and air-leak complications were also significantly higher in the second wave (P < 0.001). Conclusions: The second wave was more vicious in terms of symptoms, inflammatory markers, radiology, complications, requirement of ventilation and mortality. Mutation in the virus, lack of immunity and vaccination at the time point of second wave could have been the possible causes. The ferocity of the second wave has important implications for the government to formulate task forces for effective management of such pandemics. [ABSTRACT FROM AUTHOR]