Objectives: To describe the adaptation of a global health economic model to determine whether treatment with the angiotensin receptor neprilysin inhibitor LCZ696 is cost effective compared with the angiotensin-converting enzyme inhibitor enalapril in adult patients with chronic heart failure with reduced left ventricular ejection fraction in the Netherlands; and to explore the effect of performing the cost-effectiveness analyses according to the new pharmacoeconomic Dutch guidelines (updated during the submission process of LCZ696), which require a value-of-information analysis and the inclusion of indirect medical costs of life-years gained. Methods: We adapted a UK model to reflect the societal perspective in the Netherlands by including travel expenses, productivity loss, informal care costs, and indirect medical costs during the life-years gained and performed a preliminary value-of-information analysis. Results: The incremental cost-effectiveness ratio obtained was (sic)17,600 per quality-adjusted life-year (QALY) gained. This was robust to changes in most structural assumptions and across different subgroups of patients. Probability sensitivity analysis results showed that the probability that LCZ696 is cost-effective at a (sic)50,000 per QALY threshold is 99.8%, with a population expected value of perfect information of (sic)297,128. On including indirect medical costs of life-years gained, the incremental cost-effectiveness ratio was (sic)26,491 per QALY gained, and LCZ696 was 99.46% cost effective at (sic)50,000 per QALY, with a population expected value of perfect information of (sic)2,849,647. Conclusions: LCZ696 is cost effective compared with enalapril under the former and current Dutch guidelines. However, the (monetary) consequences of making a wrong decision were considerably different in both scenarios. Copyright (C) 2017, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.