Objective: The treatment of resistant hypertension is challenging LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, concomitantly inhibits neprilysin and blocks angiotensin type 1 receptor. Previous trials indicated that the dual actions of LCZ696 lead to further lowering of blood pressure (BP), compared with the angiotensin-receptor blocker. We therefore conducted a meta-analysis to evaluate the efficacy and safety of therapy with LCZ696 and ngiotensin-receptor blocker in patients with hypertension on major cardiovascular outcomes. Design and Method: RCTs were obtained from searches of PubMed, EmBase, and the Cochrane Library electronic databases until Feb. 2016. The effects of LCZ696 on systolic BP, diastolic BP and 24-h ambulatory BP or adverse events in patients were included for analysis. The quality assessment, sensitivity analyses, subgroup analyses, and publication biases were also conducted. Results: Five Randomized controlled trials (RCTs) included with 1927 patients were eligible. Relative to the ngiotensin-receptor blocker, LCZ696 treatment in patients decreased systolic BP (−2.70 mmHg, −4.61 to −0.80, p < 0.001), diastolic BP (2.97 mmHg, 95% CI −4.88 to −1.07, p < 0.001), 24-h ambulatory diastolic BP (−2.17 mmHg, 95% CI −3.28 to −1.06; p < 0.001), 24-h ambulatory systolic (BP −2.04 mmHg, −2.61 to −0.73, p < 0.001). No cases of angio-oedema were reported, only three serious adverse events occurred, of which none was judged to be related to the study drug, and no patients died. The LCZ696-based regimen was generally well-tolerated and could present a treatment option for hypertension inpatients especially in effective BP reduction. Conclusions: Compared with ARB, LCZ696 has proved to be a potent, effective antihypertensive agent, complementary and fully additive reduction of blood pressure. LCZ696 was shown to be safe and well tolerated.