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Objective: Clinical trial data on sacubitril/valsartan are important. Considering that real-world data have important clinical implications, we aimed to report the efficacy and safety of sacubitril/valsartan in patients with heart failure (HF) in Saudi Arabia.Methods: This was a pilot prospective clinical trial consisting of adult patients (≥18 years old) with HF (left ventricular ejection fraction [EF] ≤40%) who were taking angiotensinconverting enzyme inhibitors or angiotensin II receptor blockers for at least 1 month before presenting to the clinic and who were eligible for sacubitril/valsartan. Results: A total of 20 patients with a mean age of 60.75 years (range, 33--81 years) were included. At presentation, the majority of the patients presented with New York Heart Association (NYHA) class II symptoms (15/20), EF <30% (16/20), and ischemic etiology (15/20). After sacubitril/valsartan treatment initiation, most patients symptomatically improved to a lower NYHA class by 6 months, which was maintained until 12 months. N-terminal pro-B-type natriuretic peptide decreased from baseline at 6 and 12 months. During follow-up, no serious adverse events were reported. Complete echocardiogram data were available; however, no change in echocardiogram parameters was observed. Conclusions: In a real-world setting, sacubitril/valsartan improved HF symptoms, maintained acceptable resting heart rates, did not affect blood pressure, and did not lead to serious adverse events. [ABSTRACT FROM AUTHOR]