Objective: To assess the effectiveness and safety of nirmatrelvir-ritonavir in the treatment of mild-to-moderate COVID-19 caused by the omicron BA. 2. 2 variant. Methods: An observational study was conducted retrospectively to review the outcomes of mild-to-moderate COVID-19 patients admitted between 26 April and 30 June, 2022. Patients’ baseline characteristics were collected and assessed. Participants in the intervention group were administered nirmatrelvir-ritonavir in addition to standard care, whereas those in the control group only received standard care. The primary outcome was the duration between symptoms onset or the initial positive RT-PCR test and the subsequent conversion to a negative result. Results: The analysis included 324 patients who were administered nirmatrelvir-ritonavir and an equal number of control patients. The patient characteristics in both groups were evenly matched. The average duration from symptoms onset or the initial positive RT-PCR to negative conversion was similar in both groups (16.2±5.0 vs. 16.1±6.3 days, P=0.83). Control patients exhibited slower conversion in comparison to patients who received nirmatrelvir-ritonavir treatment within 10 days of symptom onset. Conclusion: These findings suggest that administering nirmatrelvir-ritonavir within 10 days of symptom onset could potentially reduce the time it takes for SARS-CoV-2-infected patients to negative RT-PCR results, thereby expanding the current usage guidelines for nirmatrelvir-ritonavir.