Renin-angiotensin system blockade (RAB) is the cornerstone in the management of patients with heart failure. However, the benefit of RAB in patients with accompanying severe renal impairment is not clear. We aimed to examine the effect of RAB and the differential effect of RAB depending on renal replacement (RR) in patients with severe renal insufficiency and acute heart failure. Among 5625 patients from the Korean Acute Heart Failure registry, 673 in-hospital survivors (70.9 ± 12.8 years, 376 men) who had left ventricular ejection fraction < 40% and estimated glomerular filtration rate < 30 mL/min/1.73 m2 during hospitalization were analyzed. The inverse probability of treatment weighting (IPTW)-adjusted survival analysis was used to compare the composite of all-cause mortality and rehospitalization between patients with and without pre-discharge RAB. A total of 334 (49.6%) adverse events were observed during the 1-year follow-up. The IPTW-adjusted Kaplan-Meier survival analysis showed that the 1-year event rate was 48.7% and 53.8% for patients with RAB and those without, respectively (log rank p = 0.048). RAB was significantly related to better prognosis in patients receiving RR therapy (hazard ratio HR = 0.436 0.269–0.706, p = 0.001), but not in patients not receiving RR therapy (HR 0.956 0.731–1.250, p = 0.742) in a weighted cohort (p for interaction = 0.005). Early RAB treatment in patients with heart failure and severe renal insufficiency was related to better prognosis. The benefit of RAB was particularly prominent in patients receiving RR therapy. •Renin-angiotensin blockade (RAB) was associated with favorable prognosis.•RAB was more effective in patients with renal replacement therapy (RR).•Patients with RR were taking higher intensity of RAB at 1-year follow-up.