OBJECTIVES: The focus of this assessment is to elucidate the incremental clinical effectiveness and value of PCSK9 inhibitors as adjunctive therapy to high intensity statins, compared to statin monotherapy to determine their therapeutic role in cardiovascular risk management. METHODS: A Markov model was used to evaluate the long-term costs and outcomes of adjunct PCSK9 inhibitor therapy to background statin therapy compared to high intensity statin monotherapy in multiple risk groups. Model parameters such as treatment efficacy, LDL Cholesterol (LDL-C) achievement rates, cardiovascular risk, survival, utilities, and costs were derived from large clinical trials and meta-analyses, and other published sources. Cardiovascular event rates were adjusted based on absolute LDL-C reductions and applied to each respective risk category. Costs were valued in USD 2016, and costs and benefits were discounted at a rate of 3% per annum. RESULTS: Over a time horizon of 30 years, the incremental costs per QALY of adjunct PCSK9 inhibitor therapy were $601,038.10 $562,695.71, and $487,111.46 for coronary heart disease (CHD), CHD equivalent, moderate risk cohorts, respectively. The results of this model were most sensitive to changes in PCSK9 inhibitor cost, statin adherence, and relative risk reduction for CHD death and any CRV. CONCLUSIONS: The results of this model lead us to conclude intensive LDL-C reduction may not be a cost-effective strategy for the prevention of major vascular events. Despite inferior target LDL-C goal achievement rates, high-intensity statin monotherapy was just as effective in preventing major vascular events across all risk groups. However, initiating intensive LDL-C reduction earlier in lower risk patients to prevent further decline in cardiovascular health could be a more cost-effective strategy for cardiovascular risk management. Finally, the PCSK9 inhibitors may demonstrate value in high risk statin intolerant patients, but their current therapeutic role as an adjunct therapy limits this potential.