INTRODUCTION: The monarchE trial demonstrated that the addition of 2 years of abemaciclib to adjuvant endocrine therapy (ET) significantly reduced the risk of disease recurrence in patients with hormone receptor positive (HR+), and human epidermal growth factor receptor 2-negative (HER2-), node-positive early breast cancer (EBC) at high risk of disease recurrence. Abemaciclib meets a critical unmet need for more effective adjuvant therapy for this patient population. This study evaluates the cost-effectiveness (CE) of abemaciclib plus ET compared to ET alone. METHODS: A five-state cohort transition model, which presents a United Kingdom (UK) perspective, is parameterized using data from the monarchE trial and literature. Cost-effectiveness results are presented in terms of cost/quality-adjusted life year (QALY) over a lifetime time horizon. Various assumptions were tested through sensitivity and scenario analyses and uncertainty was assessed through probabilistic analysis. RESULTS: Patients receiving abemaciclib plus ET were predicted to experience higher QALYs (11.16 compared to 10.42) at an increased cost (£87,541 compared to £48,625), leading to an incremental cost-effectiveness ratio (ICER) of £52,317 per QALY gain compared to ET alone. The increased costs associated with the addition of abemaciclib were partially offset by a reduction in distant disease recurrence and associated costs. The scenario and sensitivity analyses supported robust base case results. CONCLUSION: Despite the ICER exceeding usual willingness-to-pay (WTP) levels in the UK, a consequence of using list prices, the CE model utilizing the latest data cut from the monarchE trial, demonstrated that the upfront cost of abemaciclib reduces the risk of a terminal breast cancer prognosis and its associated cost and quality of life impact. The addition of 2 years of abemaciclib provides an option for the treatment of HR+, HER2-, node-positive, high-risk EBC.