OBJECTIVES: To explore the cost-effectiveness of mavacamten + beta-blocker/calcium channel blocker therapy (BB/CCB) versus BB/CCB monotherapy for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM). MATERIALS AND METHODS: A 5-state Markov model (New York Heart Association classes I-IV, death) that included treatment sequencing was developed. It used a Dutch societal perspective and lifetime horizon stratified into short-term (mavacamten + BB/CCB: 30 weeks; BB/CCB: 46 weeks) and long-term (i.e. post short-term) periods. The model population reflected the EXPLORER-HCM trial intention-to-treat population. Model parameters were aligned with 2016 Zorginstituut Nederland guidelines, including annual discount rates of 4.00% and 1.50% for costs and health outcomes. Costs (2022/2023 Euros), life-years (LYs) and quality-adjusted LYs (QALYs) per patient, incremental costs and LYs/QALYs, and incremental cost-utility ratios were estimated. Sensitivity and scenario analyses were conducted to evaluate the robustness of the results. RESULTS: Treatment with mavacamten + BB/CCB resulted in an incremental discounted gain of 3.09 QALYs and 3.17 LYs versus the BB/CCB monotherapy strategy. Incremental discounted costs were €49,388 over a lifetime; the additional costs of mavacamten were driven by increased treatment acquisition costs but partly offset by savings in healthcare resource utilization and indirect costs, particularly informal care costs. Mavacamten + BB/CCB was cost-effective at a €50,000 per QALY threshold versus BB/CCB monotherapy at €15,961 per QALY gain. The deterministic and probabilistic sensitivity and scenario analyses supported the robustness of the model results. CONCLUSIONS: In the Netherlands, mavacamten + BB/CCB is a cost-effective treatment strategy for symptomatic obstructive HCM compared to BB/CCB monotherapy. Obstructive hypertrophic cardiomyopathy (HCM) is a heart condition where the heart muscle becomes thick and blocks blood flow, impacting quality of life. Patients can have various symptoms including shortness of breath and fatigue.In recent years, a drug class called cardiac myosin inhibitors (CMI), has been tested in patients with symptomatic obstructive HCM, leading to approval for mavacamten (the first CMI) by the European Medicines Agency in 2024.This study aimed to compare mavacamten in combination with standard of care (SoC) vs SoC alone for patients with symptomatic obstructive HCM in the Netherlands. A model to assess cost-effectiveness was developed, to compare costs and health benefits, including length and quality of life, for these interventions over a patient’s lifetime. These cost-effectiveness estimates assist decision makers in selecting the treatment providing the best health outcomes for the lowest cost (i.e. good value for money). The model inputs are aligned with the Dutch guidelines.This study found patients live longer and have a better quality of life when treated with mavacamten compared to with SoC alone. Although treatment with mavacamten results in additional costs (€49,388 over a lifetime), patients should expect to live on average 3.17 years longer (3.09 when adjusting for quality of life). The cost per quality-adjusted life year gained is €15,961, which is considered good value for money in the Netherlands.The results of this study imply mavacamten offers meaningful health benefits for a reasonable cost, making it a valuable addition to the healthcare system in the Netherlands.