The optimal use of sacubitril/valsartan in clinical practice needs further investigation, in particular for patients with multiple comorbidities, as such patients are usually poorly represented in clinical trials. To this end, well-documented case reports may add further evidence to the bulk of “field practice” experience on sacubitril/valsartan. We report here the case of a patient with heart failure with reduced ejection refraction with multiple comorbidities treated with sacubitril/valsartan. Overall, sacubitril/valsartan led to a prompt (within a few months) improvement in LVEF (+15%, from 38 to 53%), without any noticeable adverse events. This therapy also allowed the patient to discontinue furosemide.