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To estimate the cost-effectiveness of olaparib after being funded by the Spanish National Health Service (SNHS) as first-line monotherapy maintenance treatment in patients with advanced high-grade serous ovarian carcinoma (HGSOC) and BRCA mutations in Spain. A semi-Markov model with one-month cycles was adapted to the Spanish healthcare setting, using the perspective of the SNHS, and a time horizon of 50 years. Two scenarios were compared: receiving olaparib vs. no maintenance treatment. The model comprised four health states and included the clinical results of the SOLO1 study, along with the direct healthcare costs associated with the use of first-line and subsequent treatment resources (2020 €). A discount rate of 3% was applied for future cost and quality-of-life outcomes. A probabilistic sensitivity analysis (PSA) was also carried out and a cost-effectiveness threshold of €25,000 per quality adjusted life year (QALY) was considered. The introduction of olaparib as a first-line maintenance treatment for advanced HGSOC patients with BRCA mutations implied a cost of €131,614.98 compared to €102,369.54 without olaparib (difference: €29,245.44), with an improvement of 2.00 QALYs (5.56 and 3.57, respectively). Therefore, olaparib is cost-effective for advanced HGSOC patients with BRCA mutations, with an incremental cost-effectiveness ratio of €14,653.2/QALY. The results from the PSA showed that 92.1% of the simulations fell below the €25,000/QALY threshold. The model showed that olaparib could improve the overall survival by 2 years, vs. no maintenance treatment. Olaparib as first-line maintenance treatment is cost-effective in advanced HGSOC patients with BRCA mutations in Spain. • Our results suggest that olaparib could delay disease progression and improve OS by 2 years vs. no maintenance treatment. • Treatment with olaparib resulted in a gain of 2.00 QALYs vs. no maintenance treatment, at an ICER of €14,653,2/QALY. • First-line maintenance with olaparib is cost-effective in advanced HGSOC patients with BRCA mutations in Spain. [ABSTRACT FROM AUTHOR]