OBJECTIVES: Some recent pharmacological evaluations support that higher exposures of oseltamivir may further reduce duration of influenza viral shedding and symptoms. This study investigated the economic impact of oseltamivir standard (75 mg BID) and high (150 mg BID) dose treatment and its potential in supporting pandemic influenza planning decisions in the US.  METHODS: A health economic (HE) decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - transmission dynamic model which simulated the infected population in an influenza outbreak under different scenarios.  A cost-utility analysis, under the US societal perspective, was conducted; comparing oseltamivir 150mg versus approved 75mg BID, and no treatment, three levels of uptake (25%, 50%, and 80%), for a strain with comparable virulence to typical seasonal-influenza. Model parameters such as probabilities, costs (2013 USD), lengths of stay, and utilities were derived from published studies. In the HE model, an infected patient was either treated with oseltamivir in the outpatient setting or admitted into the hospital, leading to no complications, pneumonia, sepsis, and acute respiratory distress syndrome. Total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were determined over one-year time horizon. Sensitivity analyses were undertaken. RESULTS:  Under low virulence and low transmissibility scenarios, in comparison with no treatment, the use of 75mg BID oseltamivir showed cost-saving of USD 31-33 million million and 395-452 QALY gained for 25% and 80% uptake, respectively. Compared to no treatment, oseltamivir 150 mg BID saved USD 21-32 million and 418-456 QALY gained for 25% and 80% uptake. The results were sensitive to the proportion of inpatient presentation at ED and utility during influenza. CONCLUSIONS:  Results clearly demonstrate that both 75 mg BID standard and 150 mg BID high dose oseltamivir therapy are cost saving. The findings corroborate antiviral therapy as being a valuable component of pandemic influenza planning decisions in the US.