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The duration of viral shedding is an important determinant of infectivity and transmissibility and provides vital information for effective infection prevention and control. However, few studies have evaluated viral shedding in patients admitted to hospital with 2009 H1N1 influenza and treated with oseltamivir.To determine the incidence of prolonged 2009 H1N1 influenza viral shedding in patients treated for 5 days with oseltamivir and to identify factors that promote prolonged viral shedding.This was a prospective, observational cohort study of 173 patients infected with 2009 H1N1 influenza (confirmed by RT-PCR) who were admitted to isolation rooms in the emergency department of our hospital between August 25, 2009 and December 31, 2009. All of the patients were treated according to institutional protocols and received routine follow-up RT-PCR testing after 5 days of oseltamivir therapy. Prolonged viral shedding was defined as a positive follow-up RT-PCR result.Of the 173 patients in our cohort, 88 (50·8%) showed persistent viral shedding after oseltamivir treatment. Viral shedding was significantly prolonged if antiviral therapy was started ≥2 days after symptom onset (OR 2·74, 95% CI 1·29–5·82), if there were major comorbidities (OR 3·07, 95% CI 1·29–7·32), and/or if respiratory symptoms were still present on the day 5 of antiviral treatment (OR 4·13, 95% CI 2·10–8·11).The presence of major comorbidities, a delay in initiating antiviral treatment, and continuing respiratory symptoms after 5 days of antiviral treatment are associated with prolonged shedding of the 2009 H1N1 influenza virus.