OBJECTIVES: PARADIGM-HF, a phase III trial conducted in patients with heart failure (HF), showed that sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor for treatment of HF with reduced ejection fraction (HFrEF), provided incremental cardiovascular and overall survival benefit versus enalapril. This analysis aims to quantify the number of potential all-cause deaths that could be avoided with optimal usage of sacubitril/valsartan in the treatment of HFrEF in Chile. METHODS: Data from the Instituto Nacional de Estadísticas was used to identify patients with heart failure for whom sacubitril/valsartan would be indicated, and a literature review was conducted to determine the prevalence of HF, the proportion of those NYHA Class II-IV and finally, the proportion of patients with HFrEF. The number needed to treat (NNT) to avoid one death, standardized to 12 months, was derived from the PARADIGM-HF trial. The potential number of deaths prevented or postponed as a result of sacubitril/valsartan treatment was estimated along with multi-way sensitivity analysis. The main outcome measure was all-cause mortality. RESULTS: The 2017 population (≥ 20 years) in Chile was estimated at 13,413,474 and the estimated prevalence of HF was 2%. The percentage of patients diagnosed with HF in Chile was 80%. Of these, 75% were classified as NYHA Class II-IV, 48% of whom had HFrEF. This equated to 77,262 patients for whom sacubitril/valsartan may be indicated. The absolute reduction in mortality in PARADIGM-HF was 2.8% over an average follow-up time of 27 months with a NNT standardized to 12 months of 80.3. Thus, optimal usage of sacubitril/valsartan therapy was estimated to prevent 962 deaths each year. CONCLUSIONS: The findings from this analysis suggest that a substantial number of deaths could potentially be prevented by optimal implementation of sacubitril/valsartan therapy. Thus, implementation of sacubitril/valsartan into routine clinical practice may substantially improve clinical outcomes in HFrEF patients in Chile.