This study aimed at analyzing the clinical profile of real-world patients with heart failure with reduced ejection fraction (HFrEF) and evaluating the safety and efficacy of sacubitril/valsartan among Asian patients in daily practice. We conducted a single-center prospective observational cohort study of HFrEF patients treated with sacubitril/valsartan from September 2017 to September 2018 with a follow-up of 6 months. The mean (SD) age of the 110 patients enrolled was 59.7 ± 13.3, 85 (77.3%) were men and 41 (37.3%) had ischemic cardiomyopathy. Thirty-one (27.2%) patients with low systolic blood pressure initiated sacubitril/valsartan on a tiny dose of 12/13 mg. Despite the low mean daily dose achieved in real world mainly because of hypotension, left ventricular ejection fraction increased significantly from 35.4 ± 8.9% at baseline to 43.0 ± 12.2% after 6-month follow-up (P < 0.001). We also observed a significant improvement in a 6-minute walk test (6-MWT) distance and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration reduction. No severe adverse event was recorded. Low dose sacubitril/valsartan induces beneficial cardiac reverse remodeling and improves clinical functional performance in real-world HFrEF patients without severe adverse effect. A tiny initial dose may enhance tolerability and reduce discontinuation rate by minimizing hypotension events in patients with low systolic blood pressure. These data further support using low-dose sacubitril/valsartan among eligible patients with HFrEF in Asia.