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Our aim is to describe the characteristics of the patients receiving sacubitril/valsartan (SV) in daily clinical practice. This is a prospective registry in 10 hospitals including all patients who started SV in everyday clinical practice. From October 2016 to March 2017, 427 patients started treatment with SV. The mean age was 68.1 ± 12.4 years, and 30.5% were women (22.0% in PARADIGM-HF, P < 0.001). Comparing our cohort with patients included in PARADIGM-HF, baseline treatment was different, with a lower ratio of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (2.7 vs. 3.5, P < 0.001), and a higher proportion of patients with implantable cardioverter defibrillator (53.8% vs. 15%, P < 0.001), and cardiac resynchronization therapy (25.8% vs. 5%, P < 0.001). Treatment with mineralocorticoid receptor antagonists was more frequent (76.7% vs. 60.0%, P < 0.001), and the use of beta-blockers was similar (94.6% vs. 93.0%, P = 0.43). We observed more patients in functional class III-IV (30.4 vs. 24.8, P = 0.015), higher levels of Nt pro-BNP [3421 (904–4161) vs. 1631 (885–3154) pg/mL] and worse renal function (creatinine level 1.3 ± 0.7 vs. 1.1 ± 0.3 mg/dL, P < 0.001). In real life, patients receiving SV have a higher risk profile than in the pivotal trial, poorer functional class, higher levels of natriuretic peptides, and worse renal function.