Adults 65 years and older (hereinafter referred to as seniors) are at greater risk for complications following influenza infection compared with younger adults, due to decreased vaccine efficacy and increased prevalence of chronic medical conditions with increasing age. Currently in the U.S., two influenza vaccines are licensed exclusively for use in seniors: a high-dose influenza vaccine (HD-IIV3) and an adjuvanted influenza vaccine (aIIV3). HD-IIV3 aims to improve protection through quadrupling the antigen dose per influenza strain, whereas aIIV3 is a standard-dose vaccine (SD-IIV3) to which an oil-in-water emulsion of squalene oil is added. HD-IIV3 is often offered at a price premium compared to SD-IIV3 and aIIV3. In this thesis we attempted to answer if this premium is worthwhile. We studied two specific sub-populations in the United States – Veterans receiving care through the Veterans Health Administration (VHA) and members of a large national managed care company affiliated with Optum. For our analyses we used real-word data (RWD): health insurance claims data and electronic medical records from VHA, Medicare and Optum. The availability of large databases with data of millions of people makes affordable retrospective cohort studies possible but introduces unique challenges when trying to find causal relationships. We discuss the causal interpretation of rate-change methods and propose a novel approach to test its sensitivity to violations of underlying assumptions. We conclude that HD-IIV3 is associated with less hospitalizations compared to SD-IIV3 and aIIV3. The avoided hospitalization costs offset HD-IIV3’s higher price and resulted in net cost savings.