OBJECTIVE: International guidelines recommend the introduction of sacubitril/valsartan (Entresto) in patients with heart failure (HF) and reduced ejection fraction (EF), who remain symptomatic, despite optimal uptitrated therapy. The purpose of the following analysis is to verify the real-life eligibility for sacubitril/valsartan in a population of patients suffering from chronic HF, regularly monitored in a single HF clinic and treated according to guideline-directed medical therapy (GDMT). METHODS: From a total of 1070 patients regularly monitored in our HF Clinic between January 2011 and September 2017, the clinical records of 224 patients with HF and reduced EF on optimized GDMT were retrospectively analyzed. RESULTS: Of 224 analyzed patients, 75 improved their EF or were asymptomatic after uptitration of GDMT during follow-up; 50 were not on angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for different reasons; 13 patients had systolic blood pressure ≤100 mm Hg, so they were not eligible for sacubitril/valsartan introduction. The remaining patients were still symptomatic (NYHA ≥2), and therefore, sacubitril/valsartan introduction was indicated in these 86 patients (38.4%) of 224 enrolled. CONCLUSION: In patients with HF and reduced EF, where GDMT is appropriately achieved, indication to sacubitril/valsartan treatment is around 38%.