Abstract Aims Sacubitril‐valsartan has been shown to have superior effects over angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers in patients with heart failure (HF) and hypertension. The efficacy and safety of sacubitril‐valsartan in patients with HF are controversial. We performed a meta‐analysis of randomized controlled trials to assess and compare the effect and adverse events of sacubitril‐valsartan, valsartan, and enalapril in patients with HF. Methods and results We conducted a systematic search using PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. Randomized controlled trials involving the use of sacubitril‐valsartan in patients with HF were included. We assessed the pooled odds ratio (OR) of all‐cause mortality, cardiovascular mortality, and hospitalization for HF in fixed‐effects models and the pooled risk ratio (RR) of symptomatic hypotension, worsening renal function, and hyperkalaemia in fixed‐effects models. Of the 315 identified records, six studies involving 14 959 patients were eligible for inclusion. Sacubitril‐valsartan reduced the endpoints of all‐cause mortality and cardiovascular mortality in patients with HF with reduced ejection fraction (HFrEF) in three trials with pooled ORs of 0.83 (P = 0.0006) and 0.78 (P