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Background More than 30%of the patients admitted for acute decompensated heart failure (ADHF) in our hospital are over 80 years of age. European heart failure guidelines recommend the use of renin-angiotensin system inhibitors (RASIs) in patients with heart failure with mid-range ejection fraction (HFmrEF) or reduced ejection fraction (HFrEF). However, there is a paucity of data on the effect of RASIs in elderly patients with HFmrEF and HFrEF, because elderly patients have been excluded from large clinical trials.Purpose The aim of our study was to appreciate the effect of RASIs in elderly patients with HFmrEF and HFrEF.Methods This was a post-hoc analysis of a prospective, observational, cohort study that enrolled consecutive patients admitted with ADHF in our hospital between September 2021 and September 2023. Patients who were ≥ 80 years old, with left ventricular ejection fraction (LVEF) < 49% and discharged alive were included in the present study. RASIs were defined as either ACE inhibitors or angiotensin II receptor blockers. The primary endpoint was a composite of all-cause death and heart failure (HF) hospitalizations.Results Among 300 patients enrolled, 180 patients received RASIs at discharge and 120 patients did not. The median follow-up period was 335 days (interquartile range; 120 – 450 days). Patients receiving RASIs were younger (85.5 ± 4.2 vs. 86.2 ± 4.2 years of age, p=0.02), had a higher body mass index (BMI; 21.5 ± 3.4 vs. 20.5 ± 3.6 kg/m², p=0.009) and better renal function (eGFR; 44.2 ± 20.5 vs. 36.1 ± 18.1 ml/min/1.73m², p<0.001). Patients receiving RASIs had a higher LVEF (32.9 ± 5.3 vs. 26.5 ± 8.1%, p<0.005). The use of beta-blockers at discharge was more prevalent in patients receiving RASIs (74.6% vs. 58.4%, p<0.001), The use of mineralocorticoid receptor antagonists at discharge do not correlates with the RASIs recommandation (50.2% vs. 40.0%, p=0.09). The cumulative incidence of all-cause death or HF hospitalisation one year after discharge was significantly lower in patients receiving RASIs (38.5% vs. 60.4%, p<0.001). After adjusting for confounders, the risk of a composite of all-cause death and HF hospitalizations was significantly lower in patients receiving RASIs (adjusted hazard ratio 0.62, 95% confidence interval 0.42–0.75, p<0.001). We identify no interaction between the effect of RASIs and subgroup factors such as age, BMI, dementia, malignancy, and renal function.Conclusion Use of renin-angiotensin system inhibitors at discharge in elderly patients with heart failure and mid-range and reduced left ventricular ejection fraction HFrEF was associated with lower incidence of all-cause death or heart failure hospitalization.