OBJECTIVES: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved by the U.S. Food and Drug Administration (FDA) as cholesterol-lowering therapies for persons with familial hypercholesterolemia or atherosclerotic cardiovascular disease. However, the long-term cost-effectiveness of PCSK9 inhibitors is not clear. This study was designed to estimate the long-term health impact and economic value of PCSK9 inhibitors for older Americans (aged 51 and older). METHODS:  We conducted simulations using the Future Elderly Model (FEM), an established dynamic microsimulation model, to project the lifetime outcomes for the population aged 51+ in the United States. Health effects estimates and confidence intervals from published meta-analysis studies were used to project changes in life expectancy, quality-adjusted life-years, incidence of heart disease and lifetime medical spending resulting from use of PCSK9 inhibitors. We consider two treatment-eligibility criteria: 1) current FDA eligibility; and 2) an extended eligibility criterion that considers PCSK9 inhibitor use for persons with no pre-existing cardiovascular disease (CVD) but with high-CVD risks. RESULTS:  Utilization of PCSK9 inhibitors by individuals covered by the current FDA approval would extend life-expectancy at age 51 by an estimated 1.2 years and would yield a lifetime net value of $11,100 per capita. We also estimate that PCSK9 inhibitors would generate a lifetime net benefit of $21,000 per capita if utilization were extended to those with high-CVD risk. Looking only at the population covered by current FDA approval over the next 20 years, PCSK9 inhibitors would generate cumulative net value of $0.96 trillion. CONCLUSIONS:  Our study suggests that PCSK9 inhibitors would offer positive long-term net value for patients and the U.S. healthcare system. In addition to current FDA-approved indications, our study also suggests greater value if more people gain access to this new class of drugs.