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Limited data support high-dose oseltamivir in critically ill patients with influenza. In several recent influenza seasons, there were oseltamivir drug shortages.This was a retrospective cohort analysis of 57 patients admitted to the intensive care unit (ICU) with confirmed influenza. Patients receiving high-dose oseltamivir were compared to those receiving standard dosing.When adjusted for clinically relevant predictors of disease severity, including age, duration of therapy, Acute Physiology and Chronic Health Evaluation II score, and receipt of extracorporeal membrane oxygenation, there was no difference in the duration of mechanical ventilation, oxygenation, ICU length of stay, or hospital length of stay between the high-dose and standard dose groups.As compared to the standard doses of oseltamivir, higher-dose (ie, double dose) oseltamivir was not associated with improvement in any clinical outcomes. Using higher doses empirically on all patients during influenza season may exacerbate local drug shortages.