Non-egg-based influenza vaccines eliminate the potential for egg-adapted mutations and potentially increase vaccine effectiveness. This retrospective study compared hospitalizations/emergency room (ER) visits and all-cause annualized healthcare costs among subjects aged 4-64 years who received cell-based quadrivalent (QIVc) or standard-dose egg-based quadrivalent (QIVe-SD) influenza vaccine during the 2018-19 influenza season. Administrative claims data (IQVIA PharMetrics? Plus, IQVIA, USA) were utilized to evaluate clinical and economic outcomes. Adjusted relative vaccine effectiveness (rVE) of QIVc vs. QIVe-SD among overall cohort, as well as for three subgroups (age 4-17 years, age 18-64 years, and high-risk) was evaluated using inverse probability of treatment weighting (IPTW) and Poisson regression models. Generalized estimating equation models among the propensity score matched sample were used to estimate annualized all-cause costs. A total of 669,030 recipients of QIVc and 3,062,797 of QIVe-SD were identified after IPTW adjustments. Among the overall cohort, QIVc had higher adjusted rVEs against hospitalizations/ER visits related to influenza, all-cause hospitalizations, and hospitalizations/ER visits associated with any respiratory event compared to QIVe-SD. The adjusted annualized all-cause total costs were higher for QIVe-SD compared to QIVc ((+$461); p < 0.05).