Seasonal influenza is associated with significant healthcare resource utilization. An estimated 490,000 hospitalizations and 34,000 deaths were attributed to influenza during the 2018-2019 season. Despite robust influenza vaccination programs in both the inpatient and outpatient setting, the emergency department (ED) represents a missed opportunity to vaccinate patients at high risk for influenza who do not have access to routine preventive care. Feasibility and implementation of ED-based influenza vaccination programs have been previously described but have stopped short of describing the predicted health resource impact. The goal of our study was to describe the potential impact of an influenza vaccination program in an urban adult emergency department population using historic patient data. This was a retrospective study of all encounters within a tertiary care hospital-based ED and three freestanding EDs during influenza season (defined as October 1 - April 30) over a two-years, 2018-2020. Data was obtained from the electronic medical record (EPIC®). All ED encounters during the study period were screened for inclusion using ICD 10 codes. Patients with a confirmed positive influenza test and no documented influenza vaccine for the current season were reviewed for any ED encounter at least 14 days prior to the influenza-positive encounter and during the concurrent influenza season. These ED visits were deemed a missed opportunity to provide vaccination and potentially prevent the influenza-positive encounter. Healthcare resource utilization, including subsequent ED encounters and inpatient admissions, were evaluated for patients with a missed vaccination opportunity. A total of 116,140 ED encounters occurred during the study and were screened for inclusion. Of these, 2115 were influenza-positive encounters, which represented 1963 unique patients. There were 418 patients (21.3%) that had a missed opportunity to be vaccinated during an ED encounter at least 14 days prior to the influenza-positive encounter. Of those with a missed vaccination opportunity, 60 patients (14.4%) had subsequent influenza-related encounters, including 69 ED visits and 7 inpatient admissions. Patients presenting to the ED with influenza frequently had opportunities to be vaccinated during prior ED encounters. An ED-based influenza vaccination program could potentially reduce influenza-related burden on healthcare resources by preventing future influenza-related ED encounters and hospitalizations.