Abstract Background An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. Methods In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan. Results The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13–22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31–8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10–1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI, 1.11–88.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. Conclusions Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients. In this retrospective study of 113 patients, we were able to identify independent risk factors for prolonged viral RNA shedding in patients with COVID-19, specifically male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation.