BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors, such as evolocumab, are cholesterol-lowering drugs effective in lowering lipid levels in high-risk patients with primary hypercholesterolemia or mixed dyslipidemia. OBJECTIVE: This study assessed the cost effectiveness of evolocumab in combination with lipid-lowering therapies (LLTs) compared with LLTs alone, from a public healthcare perspective in the Kingdom of Saudi Arabia (KSA). METHODS: A Markov cohort state transition model was used, incorporating efficacy estimates from the FOURIER clinical trial and baseline cardiovascular event rates observed in clinical practice. Other model inputs were extracted from the literature and Saudi sources. RESULTS: In patients with clinically evident atherosclerotic cardiovascular disease and baseline low-density lipoprotein cholesterol ≥ 70 or ≥ 100 mg/dL, adding evolocumab to a maximally tolerated statin, with or without ezetimibe, was associated with incremental cost-effectiveness ratios (ICERs) of Saudi Arabian riyal (SAR) 109,274 ($US60,708) per quality-adjusted life-year (QALY) gained and SAR75,163 ($US41,757) per QALY gained, respectively. The ICER was SAR22,391 ($US12,440) per QALY gained in patients with heterozygous familial hypercholesterolemia. Sensitivity analysis results were robust to changes in model parameters and fell below the willingness-to-pay threshold of up to three times gross domestic product per capita in 2019 (SAR264,813 [$US147,118]). CONCLUSION: Evolocumab can be considered a cost-effective treatment option for patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia in the KSA.