To analyze the cost-effectiveness of sacubitril/valsartan versus usual care in heart failure with reduced ejection fraction (HFrEF) for patients classified as New York Heart Association (NYHA) Class II-IV, in Colombia. Previously developed UK cost-effectiveness model based on PARADIGM-HF (McMurray, 2014) trial was adapted to Colombia using the Latin-American trial subgroup (N=1,433) and Colombia-specific epidemiologic and economic data to assess the impact of sacubitril/valsartan versus usual care (ACEi). A (Markov) cost-utility model structured as a regression-based cohort model with one-month cycling was utilized to examine a hypothetical cohort of HFrEF patients receiving therapy. Clinical outcomes included mortality, hospitalization, and adverse events. Quality-adjusted-life years (QALY) were derived from the trial. Costs (2015 COP$) include drug, hospitalization and resource use. Primary outcome was cost-utility (cost/QALY gained) over a 30-year time horizon. Sensitivity analyses were performed. Base-case results suggest that compared with an ACEi, sacubitril/valsartan is associated with incremental costs of COP$16.6 million and 0.50 QALYs gained, resulting in an incremental cost-effectiveness ratio of COP$32.4 million per QALY gained. Increased costs of pharmacological therapy were offset by reductions in hospitalization costs. All-cause– and CV-related mortality are projected to be reduced at all time points. Expected survival is estimated to increase from 7.20 years for those receiving an ACEi to 8.11 years for a cohort of patients receiving sacubitril/valsartan. Overall, results were not sensitive to changes in model parameters; results were most sensitive to parameters used to estimate CV mortality and duration of treatment effect. The Colombia-adapted model estimates suggest that sacubitril/valsartan represents a cost-effective intervention in the treatment of HFrEF (NYHA Class II-IV) versus an ACEi, assuming a willingness-to-pay threshold of 3 times the 2015 per capita GDP in Colombia (COP$52.4 million). Consequently, sacubitril/valsartan represents reasonable value compared with other commonly accepted health care interventions.