Aims & Objectives : To compare the clinical characteristics/profiles of the patients in first and second waves of COVID-19 in India and correlate these characteristics with risk of inhospital mortality. Design: Observational analytical study with longitudinal follow-up. The clinicoepidemiological and laboratory profile of patients admitted in the second wave of COVID19 will be noted at the time of admission, and they will be followed-up during their stay in the hospital to record their outcome status. Medical records will be used to record the data of COVID-19 patients admitted in the first wave. Setting: A tertiary care centre in Bihar, India Participants: All patients who are COVID-19 positive based on positive RT-PCR test of oropharyngeal or nasopharyngeal swab and admitted to AIIMS, Patna during the study period. Outcome measures: The difference in clinic-epidemiological profile of patients admitted in AIIMS Patna during the first and second wave of COVID-19 and thus we attempted to discover the effects of multiple factors such as vaccination and mutant viruses on the profile of the 2nd wave. We could also correlate the outcome status of the patient with their clinicepidemiological profile. Results: Females were relatively more commonly affected in the second wave. Contact history was significantly higher in the second wave. Comorbidities and clinical features were mostly similar although generalized weakness and fatigue was more common in the second wave. ARDS and septic shock were less frequent in the second wave although overall mortality was slightly higher. Azithromycin, HCQ use was discontinued whereas pulse methylprednisolone started to be used frequently. Remdesevir and tocilizumab use was rationalized. HFNC and NIV were better utilized in the second wave. Mucormycosis outbreak complicated the second wave. Out of 42 individuals who were partly immunized (fourteen days after 1st dose to symptom onset), 28 patients survived. Conclusion: The rapid upsurge of cases in the second wave led to COVID affecting previously less affected strata of the population as well as higher overall mortality, although the better training of healthcare workers and understanding of the disease helped offset some of these problems.