This retrospective multicenter study compared the demographic and clinical characteristics of hospitalized COVID-19 patients across two waves at select public hospitals in Mumbai. A total of 26,405 laboratory-confirmed cases were included, excluding patients transferred to other centers. Data analysis involved chi-square tests and multivariate binomial logistic regression. Both waves showed a male preponderance (64% in wave 1, 63% in wave 2, p=0.131) and a majority of patients over 35 years (77% in wave 1, 76% in wave 2, p=0.273). Despite a higher oxygen requirement in wave 2 (23% vs. 36%, p=0.001), the fatality rate was lower (13% vs. 9%, p=0.001). Symptom burden and comorbidities were significantly lower in wave 2. Kidney involvement (p=0.001) was the strongest predictor of oxygen requirement and death in wave 1, whereas age over 55 (p=0.001) was the most consistent predictor across both waves. Hypertension and/or diabetes (p=0.001) were associated with increased oxygen requirement but not death in both waves. In conclusion, while the age and gender distribution remained similar across both waves, wave 2 had a lower fatality rate and comorbidity burden despite a higher oxygen demand. The lower fatality rate in wave 2 stands out as a striking result in this large population study, contrary to earlier speculations. Age over 55 was a consistent predictor of both oxygen requirement and mortality, while hypertension and diabetes were only predictors of oxygen need.