Objectives: As of 2019, quadrivalent influenza vaccine (QIV) has replaced trivalent influenza vaccine (TIV) in the national immunization program in The Netherlands. Target groups are individuals of 601 years of age and those with chronic diseases. The objective was to estimate the incremental break-even price of QIV over TIV at a threshold of (sic)20 000 per quality-adjusted life-year (QALY). Methods: An age-structured compartmental dynamic model was adapted for The Netherlands to assess health outcomes and associated costs of vaccinating all individuals at higher risk for influenza with QIV instead of TIV over the seasons 2010 to 2018. Influenza incidence rates were derived from a global database. Other parameters (probabilities, QALYs and costs) were extracted from the literature and applied according to Dutch guidelines. A threshold of (sic)20 000 per QALY was applied to estimate the incremental break-even prices of QIV versus TIV. Sensitivity analyses were performed to test the robustness of the model outcomes. Results: Retrospectively, vaccination with QIV instead of TIV could have prevented on average 9500 symptomatic influenza cases, 2130 outpatient visits, 84 hospitalizations, and 38 deaths per year over the seasons 2010 to 2018. This translates into 385 QALYs and 398 life-years potentially gained. On average, totals of (sic)431 527 direct and (sic)2 388 810 indirect costs could have been saved each year. Conclusion: Using QIV over TIV during the influenza seasons 2010 to 2018 would have been cost-effective at an incremental price of maximally (sic)3.81 (95% confidence interval, (sic)3.26-4.31). Sensitivity analysis showed consistent findings on the incremental break-even price in the same range.