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Abstract Background and Aims The effectiveness of coronavirus disease 2019 (COVID‐19) vaccines in reducing symptoms, disease advancement, complications, and mortality in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has been well‐established. This case‐control study aimed to compare different blood parameters, and prognostic and survival outcomes of COVID‐19 patients based on vaccination status. Methods We performed a case‐control study that included hospitalized patients with COVID‐19 at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Individuals who received vaccination were designated as cases and unvaccinated individuals as controls. Demographics, co‐morbidity, clinical data, laboratory data, and disease outcomes were recorded for both groups. Multivariate, Cox, and linear regression were used for analysing blood parameters, hospital admission, survival, and hospital stay, respectively, between cases and controls. Results Out of 100 participants enrolled, 46 were vaccinated, and 54 weren't. At admission, ferritin and erythrocyte sedimentation rate (ESR) were significantly lower in cases. At discharge, cases showed a higher monocyte than controls. Ferritin, ESR, and d‐imer showed excellent performance in determining the severity of symptoms. Significant correlation and regression of ferritin and ESR with the length of hospital stay was observed. Length of hospital stay was significantly lower in cases than in controls. No significant differences between cases and controls were observed in mortality. Conclusion COVID‐19 vaccines effectively reduced hospitalization duration. Ferritin and ESR were significantly lower in vaccinated individuals and showed the best utility in monitoring the disease.