Background and aim: Coronavirus disease 2019 (COVID-19) has spread rapidly all over the world and has become a pandemic. Although negative reports have been reported about the use of hydroxychloroquine (HCQ) in patients with moderate to severe disease and hospitalized COVID-19 patients, its effect on RT-PCR negativity is unknown, mostly in mild disease and outpatients. In this study, the effects of HCQ and favipiravir on RT-PCR negation were compared. Methods: In this multicenter, retrospective, cross-sectional study, consecutively presenting COVID-19 patients who were positive for RT-PCR between 13 March 2020 and 15 January 2021 were analyzed. Negative RT-PCR results and times were recorded in the follow-up of the patients. All of the patients included in the study consisted of heathcareworkers and the patients were divided into two groups as HCQ or favipiravir users. Results: The favipiravir and HCQ patient groups were similar in terms of age, gender, comorbidities, and hospitalization rate. The median number of PCR-negative cases on the seventh day of treatment was significantly higher in the HCQ group (p = 0.007). The median RT-PCR negation time was 9 days in the HCQ group versus 10 days in the favipiravir group (p = 0.006). Conclusion: The use of HCQ shortens the RT-PCR negative time compared to favipiravir in patients who are in the relatively young age group and have a definite diagnosis of COVID-19. This result is important in terms of viral spread and contamination. There were no side effects that required a change in treatment in either drug group.