Study Objective: Seasonal Influenza continues to present a significant annual burden as the vaccination rate for all persons six months and older in the United States is 51.8%. Emergency Department (ED) based influenza programs have been successfully implemented and improve vaccine uptake, reduce incidence and costs, as well as improve outcomes. We modeled the process of implementing an ED based vaccination program for a large health system's Medicare (65+) and Medicaid populations. We utilized existing electronic health records (EHR) and evaluated the impact on the patient population and expenditures to health system.Methods: A retrospective review of ED encounters limited to Medicare and Medicaid populations was performed across 14 tertiary care hospital EDs and 6 freestanding EDs for calendar year 2020. Together, the total number of unvaccinated individuals was identified to determine the potential impact of an ED vaccination campaign. The average cost and loss per inpatient stay was identified from prior industry Medicare benchmark data. Medicare benchmark data was utilized to extrapolate Medicaid losses. Results from previously published cost-effectiveness studies identified the vaccination thresholds to prevent one additional case of influenza, one additional hospitalization, and one additional fatality. A predictive model was developed to assess the total preventable flu cases, hospitalizations, fatalities, and incremental cost avoidance based on total identified unvaccinated population.Results: A total of 39,463 unvaccinated individuals were identified with 14,064 individuals classified as Medicare aged 65 and over as well as 25,379 individuals classified as Medicaid. Assuming a 95% Target Outreach, 90% Medical Eligibility, and 70% acceptance rate, 414 flu cases would be prevented (266 Medicaid, 148 Medicare), 28 hospitalizations would be prevented (18 Medicaid, 10 Medicare), and 8 deaths would be prevented (5 Medicaid, 3 Medicare). Accordingly, a reduction in admissions would prevent $409,360 in total inpatient medical costs and $36,232 in losses to healthcare systems for Influenza-related admissions.Conclusion: An ED based influenza vaccination program would have measureable impact on patient influenza disease burden and associated medical expenditures.