Background: The incidence of hypertension and clinical complications (e.g., heart, cerebrovascular and kidney injury) is increasing worldwide. It is widely known that a relatively large dose of valsartan (320 mg) could alleviate clinical complications. The current network meta-analysis assessed which drug could be combined with a relatively large dose of valsartan to control blood pressure (BP) more effectively. And which combination therapy with different dosages of valsartan did not induce excessive BP reduction with increasing dosages of valsartan. Methods: The PubMed, Embase, Medline, Cochrane Library, CNKI, Wanfang, and CSTJ databases were searched from inception to October 2022 for relevant randomized controlled trials (RCTs). The search strategies included concepts related to hypertension and two-drug combination therapy of different doses of valsartan, and there were no language or data restrictions. The outcomes included adverse effects and changes in systolic BP and diastolic BP. Permanent discontinuations related to treatment were the most accurate and objective measure of adverse effects. The common adverse effects of most studies (i.e., dizziness, headache, nasopharyngitis, asthenia and urticaria) were also included. A Bayesian network meta-analysis was performed, and mean differences with 95% confidence intervals were calculated. ADDIS and STATA were used for Bayesian model network meta-calculation. Results: Thirty-four RCTs were included involving 26,752 patients, and the interventions included different doses of valsartan combined with various types and doses of drugs. Among many combination therapies, the combination of valsartan 320 mg with amlodipine 10 mg (p 0.01) had the best antihypertensive effect without significant adverse effects. Compared with valsartan 80 mg and 160 mg, valsartan 320 mg combined with hydrochlorothiazide 25 mg (p > 0.05) did not further reduce BP and was not shown to increase the incidence of adverse effects. Conclusions: Combination therapy with a relatively large dose of valsartan could control BP and improve clinical complications effectively. However, for hypertensive patients with different treatment requirements, specific choices should be made regarding whether to control BP, treat clinical complications, or both.