OBJECTIVES: Despite multiple evidence-based therapies, HF continues to be characterized by high mortality/hospitalization rates. Sacubitril/valsartan (sac/val), a first-in-class angiotensin receptor neprilysin inhibitor treatment for HF with reduced ejection fraction (HFrEF), provided incremental cardiovascular and overall survival benefit in PARADIGM-HF over the ACE inhibitor enalapril. The objective was to quantify the number of deaths, HF hospitalizations, and 30-day HF re-admissions that potentially could be avoided with optimal usage of sac/val for the treatment of HFrEF patients in Canada. METHODS: Data from Statistics Canada was used to quantify the population above 18 years of age. A literature search was then conducted to determine the HF prevalence in Canada, the proportion of these with NYHA ClassII/III, and the proportion of HFrEF patients. The NNT to avoid one death, hospitalization, and 30-day HF re-admission, standardized to 12 months was derived from the PARADIGM-HF trial. The potential number of deaths/hospitalizations prevented as a result of optimal usage of sac/val as per current Canadian indication was estimated using multiple-way sensitivity analysis and analysis-of-extremes method. RESULTS: Canadian HF prevalence of 2.31% was applied to determine the number of HF patients; 64% were classified as NYHA ClassII/III with 56% identified as HFrEF. In Canada, ~242,200 patients are affected with HFrEF, NYHA ClassII/III. Based on a NNT of 80, optimal usage of sac/val therapy was estimated to prevent 3,016 deaths and 3,016 hospitalizations/ year (range, 1,930–4,331). With a NNT of 61, a total of 3,984 30-day re-admissions/year (range, 2,546-5,744) would be prevented. CONCLUSIONS: This analysis suggests that a substantial number of deaths, hospitalizations, and 30-day re-admissions in Canada could potentially be avoided by optimal usage of sac/val therapy. It supports the importance of implementing evidence-based therapy into routine clinical practice to improve clinical outcomes for HFrEF patients in Canada as the hospitalization and mortality rates still remain elevated.