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 compared with enalapril. This analysis aims to quantify the number of all-cause deaths that could be avoided with optimal usage of sacubitril/valsartan in the treatment of HFrEF in Mexico. METHODS: Data from INEGI Population 2010 Report and Projections was used to quantify the target population. A literature review was conducted to determine the prevalence of HF, and the proportion of HFrEF patients classified as NYHA Class II-IV, in Mexico. The number needed to treat (NNT) to avoid one death due to any cause, standardized to 12 months, was derived from the PARADIGM-HF trial. The potential number of deaths prevented or postponed with sacubitril/valsartan treatment was estimated along with multiple-way sensitivity analysis. The main outcome measure was all-cause mortality. RESULTS: The 2017 population (≥18 years) in Mexico was estimated at 82,206,974 and the estimated prevalence of HF was 2.3%. Further, the percentage of HF registered episodes in the National Health System was 41.1%, yielding approximately 765,668 patients. Half of these patients had HFrEF; 85.0% of whom were NYHA Class II-IV. This equated to 326,986 patients with HFrEF NYHA II-IV. Finally, the absolute reduction in mortality in PARADIGM-HF was 2.8% over an average follow-up time of 27 months. This translates into a NNT, standardized to 12 months, of 80.3. Thus, optimal usage of sacubitril/valsartan therapy was estimated to potentially prevent 4,072 deaths each year. CONCLUSIONS: The findings from this analysis suggest that a substantial number of all-cause deaths could potentially be prevented with optimal implementation of sacubitril/valsartan therapy. Implementation of sacubitril/valsartan into routine clinical practice is important, and may substantially improve clinical outcomes among HFrEF patients in Mexico.