OBJECTIVES: Vaccines have been the main global means to minimize the impact of influenza and are recommended by WHO for individuals aged 65 years or older. The primary goal of influenza vaccination in the elderly is to reduce the risk of complications. Since 1998, a public-funded trivalent influenza vaccine (TIV) vaccination program has been implemented by the Taiwan government targeting people aged over 65 years. Another proposed alternative for preventing seasonal influenza is quadrivalent influenza vaccine (QIV) which contains two influenza A-lineages and two influenza B-lineages. The aim of the study is to assess, from the governmental perspective, the cost-effectiveness of adopting QIV versus TIV for the elderly aged 65 years or older. METHODS: A Markov model was used to estimate the cost and effectiveness of QIV and TIV in the elderly. Direct cost data was obtained from the Taiwan National Health Insurance claims data. Vaccine efficacy and coverage rate were based on government statistical reports. Outcomes of lifetime included cases, utilizations, and deaths avoided and QALYs gained. The corresponding incremental cost-effectiveness ratios (ICERs) were also estimated. The discount rate of cost and effectiveness was set at 3.5%. RESULTS: Compared to TIV, adopting QIV would yield the influenza-related outcomes as follows: 26,319 influenza cases avoided, 26,021 cases of outpatient visit avoided, 2,771 cases of influenza complication avoided, and 330 deaths avoided. Using QIV instead of TIV would bring an additional 19,310,320 QALYs at an extra cost of US$223.39 billion, yielding an ICER of US$35,851.3 per QALY gained. When herd protection of vaccination is considered, the ICER would reduce to US$32,660.1 per QALY gained. CONCLUSIONS: To use QIV as an alternative of first-line strategy to prevent seasonal influenza for the elderly in Taiwan would be cost-effectiveness from the governmental perspective.