IMPORTANCE Preliminary cost-effectiveness analyses of proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) were based on benefits estimated from reductions in low-density lipoprotein cholesterol that occurred in PCSK9i trials with variable results. The recent Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial provides better information about the effectiveness of the drug. OBJECTIVE To use the trial results to determine the cost-effectiveness of a PCSK9i and statin treatment strategy compared with a statin alone strategy. DESIGN, SETTING, AND PARTICIPANTS We derived observed rates of events, outcomes, cost of care, and health insurance from existing literature for a theoretical cohort of patients designed to resemble the FOURIER PCSK9i trial population and created a Markov model during the time horizon of a full lifetime. MAIN OUTCOMES AND MEASURES We evaluated the incremental cost-effectiveness ratio from a health system perspective, and the return on investment from a private payer perspective. For both measures, we assumed an annual PCSK9i drug price of 14 300, with a lapse in US patent protection that would reduce the price by 43%in year 12. Costs were reported in 2016 US dollars. RESULTS This study modeled 1000 hypothetical patients with attributes similar to those of the FOURIER trial cohort. At the current price, the incremental cost-effectiveness ratio of statin plus PCSK9i therapy was 337 729 per quality-adjusted life-year. Our probabilistic sensitivity analysis found that a statin plus PCSK9i strategy had a low probability (<1%) of being cost effective at the commonly accepted societal threshold of 100 000 per quality-adjusted life-year. Furthermore, PCSK9i produced a negative return on investment of 86%for private payers. In our threshold analysis, the price of PCSK9i would need to drop 62%, to 5459 per year, to reach 100 000 per quality-adjusted life year. CONCLUSIONS AND RELEVANCE At current prices, the addition of PCSK9i to statin therapy is estimated to provide an additional quality-adjusted life year for 337 729 . Significant discounts are necessary to meet conventional cost-effectiveness standards.