OBJECTIVES: This analysis was conducted to demonstrate potential downstream healthcare cost savings as a result of increasing vaccination rates for influenza in the United States. METHODS: An age-structured susceptible-exposed-infectious-recovered (SEIR) compartmental model was constructed to model the course of influenza infection over the course of 1 year in the United States.  A realistic age structure was incorporated using mixing rates between age groups from the European POLYMOD survey. The SEIR model was adapted to include another compartment for vaccination.  A series of difference equations was used to model transitions to and from each compartment.  Time-dependent vaccination rates were obtained using monthly estimates of vaccination rates obtained from the Centers for Disease Control and Prevention (CDC).  Cost and healthcare utilization data were obtained from the existing literature, and included outpatient visits, hospitalization, and antiviral drug treatment.  Costs were reported in 2013 U.S. dollars. Microsoft Excel 2011 was used to conduct the analysis.  RESULTS: Under a base case vaccination rate of 40 percent, an estimated 11 percent of individuals in the United States were projected to have symptoms of influenza infection. Healthcare costs attributable to influenza infection were estimated to be $13.6 billion. Increasing vaccination rates to 50 percent decreased the percentage of symptomatic individuals to approximately 7 percent, resulting in downstream healthcare costs of $9.5 billion.  Further increasing vaccination rates to 60 percent is projected to further reduce downstream healthcare costs to approximately $5.0 billion. CONCLUSIONS: This exploratory analysis demonstrates that significant healthcare cost savings can be realized by increasing vaccination rates for influenza in the population.