AimSacubitril/valsartan has been demonstrated to reduce blood pressure in hypertensive patients, but the best dose remains unclear. We performed this network meta-analysis to determine the comparative efficacy and safety of three available doses of sacubitril/valsartan (i.e., 100, 200, and 400 mg).Methods and resultsWe searched four databases for relevant studies published before January 2022. Mean systolic and diastolic blood pressures in the sitting position (msSBP and msDBP) and ambulatory condition (24-h maSBP and maDBP) and adverse events (AEs) were assessed. Nine randomized controlled trials (RCTs) involving 5474 patients were included. Sacubitril/valsartan 200 mg once daily was slightly better than 400 mg once daily in lowering 24-h maDBP (MD, 1.31 mmHg; 95% CI 0.61–2.01 mmHg), slightly better than 100 mg once daily in lowering 24-h maSBP (MD, − 3.70 mmHg; 95% CI  − 6.22 to − 1.18 mmHg) and 24-h maDBP (MD, − 2.98; 95% CI − 5.11 to − 0.85), and slightly better than Valsartan 160 mg once daily in lowering 24-h maSBP (MD, − 3.23 mmHg; 95% CI, − 5.25 to − 1.21). 400 mg once daily of sacubitril/valsartan was better than 200 mg once daily in lowering msDBP (MD, − 9.38 mmHg; 95% CI − 17.79 to − 0.97 mmHg). Interestingly, 400 mg once daily of sacubitril/valsartan had fewer trial-specified AEs than 200 mg once daily (OR, 0.74; 95%CI 0.55–0.99). There was no statistical difference for the remaining comparisons.ConclusionsIn hypertensive patients, 200 mg once daily of sacubitril/valsartan may exert a greater reduction in ambulatory blood pressure than 100 mg once daily and 200 mg once daily may not be inferior to 400 mg once daily. Moreover, it is not clear that sacubitril/valsartan lowers blood pressure more than an angiotensin receptor blocker. Further trials are required to determine the incremental value of sacubitril/valsartan as an anti-hypertensive agent.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1007/s00392-022-02120-0.