Background: Peramivir, intravenous neuraminidase inhibitor, is available to treat influenza in hospitalized patients in South Korea. Whether it provides clinical benefits to the critically ill patients with severe influenza infection admitted to intensitve care unit (ICU)compared to oral oseltamivir remains unclear. Methods: From August 2009 through March 2014, Patients = 18 confirmed with laboratory evidence of influenza infection and hospitalized to medical ICU more than 24 hours were enrolled at Asan Medical Center. Study was performed retrospectively Results: Ninety six patients were enrolled; 38 and 58 received peramivir and oseltamivir initially, respectively. SOFA score was higher in patients initiated with peramivir. More clinical complications including shock (68.4 vs 44.8%), acute kidney injury (44.7 vs 22.4%) and hospital acquired pneumonia (47.4 vs 27.6%) developed in patients receiving peramivir initially. There was no difference of median duration of use of antiviral agents between two groups (10 days in both groups). More triple combination antiviral agents were prescribed in patients initiated with oseltamivir (36.2 vs 7.9%, P=0.002) while more vasopressors (78.9 vs 44.8%, P=0.001) was used in those initiated with peramivir. There were no significant differences including median length of ICU (20.5 in peramivir vs 17 days in oseltamivir, P=0.284) and 28-day mortality (36.8% [14/38] in peramivir vs 34.5% [20/58] in oseltamivir, P=0.813). Acute heart failure (Odds ratio [OR] 3.668, 95% Confidence Interval [CI], 1.134-11.870, P=0.03), hospital acquired pneumonia (OR 4.197, 95% CI, 1.578-11.161, P=0.004) and use of corticosteroid (OR 3.022, 95% CI, 1.169-7.812, P=0.022) were associated with 28-day mortality. Conclusions: Peramivir may be an optional antiviral agent to treat the critically ill patients with severe influenza infection and hospitalized to ICU.