Background: Whether there is also a correlation between viral shedding duration and the clinical course of illness in COVID-19 has not yet been determined. Methods: In this retrospective study, we included 239 adult inpatients (all ≥18 years old) with laboratory-confirmed COVID-19 from the Wuhan Tongji Hospital (Wuhan, China). Results: Of the subset of 239 patients included in this study, 33 patients died due to COVID-19 and 45 patients demonstrated clinical progression to critical illness. Patients with a long duration of viral RNA shedding as compared to short duration of viral RNA shedding also had significantly lower mortality rates ((9.5% vs. 18.6%, P= 0.04) and a lower rate of progression to critical illness (16.7% vs. 21.2%, P= 0.37). Viral RNA shedding is an independent risk factor for mortality within 28 days of observation (OR 0.94, 95% CI: 0.88-0.99, P= 0.025, by multivariable regression analyses) and increased duration of viral shedding is correlated with a significant survival advantage (P =0.047) and lower risk of progression to critical illness (P =0.029, by Kaplan-Meier analyses). Conclusions: Prolonged viral RNA shedding duration is associated with improved patient prognosis and reduces the risk of progression to critical illness in this subset of COVID-19 patients. Further clinical studies are necessary to determine if a longer duration of viral RNA shedding with COVID-19 is predictive of an overall better patient prognosis and outcome.