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Abstract Aim Migraine is a neurological disorder prevalent in Taiwan, affecting millions of individuals and imposing a substantial burden on both quality of life and societal productivity. Calcitonin gene-related peptide inhibitors, such as eptinezumab, represent a major advancement in migraine prevention; however, their high cost and the lack of local economic evaluations warrant further study. This research aims to assess the cost-effectiveness of eptinezumab, compared with placebo, for migraine prevention in Taiwan. Methods A Markov model with a six-month time horizon was developed to evaluate the cost-effectiveness of eptinezumab versus placebo. The analysis was conducted from a health payer’s perspective, incorporating clinical and economic inputs from clinical trials and the literature. Patients were categorized into six health states based on monthly migraine days. Outcomes were expressed as incremental costs per quality-adjusted life year (QALY) gained. Incremental cost-effectiveness ratios (ICERs) were estimated using a Monte Carlo simulation with 10,000 iterations, alongside deterministic and probabilistic sensitivity analyses to evaluate uncertainty. For interpretation, results were compared with Taiwan’s GDP per capita ($32,327 per QALY), and exploratory analyses also considered a threshold of three times GDP per capita ($96,981). Results Over six months, the total cost for patients receiving eptinezumab was $4,461, compared with $1,065 for placebo, with corresponding QALYs of 0.35 and 0.31, respectively. This yielded an ICER of $73,929 per QALY gained. Deterministic sensitivity analysis identified utility values for patients with varying migraine frequency as the most influential parameter, increasing the ICER to approximately $105,000 when varied, which may exceed the upper WTP threshold. Probabilistic sensitivity analysis showed that eptinezumab was cost-effective in 98% of iterations at the exploratory threshold of three times GDP per capita. Conclusion Eptinezumab was likely cost-effective for migraine prevention in Taiwan, with utility values associated with migraine frequency identified as the key driver, highlighting the need for locally relevant quality-of-life data in future evaluations.