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Background and Objective: Recently, vonoprazan‐amoxicillin (VA) dual therapy has been reported as a promising approach for Helicobacter pylori (H. pylori) eradication. However, the effects of VA therapy versus bismuth‐containing quadruple therapy (BQT) on H. pylori eradication remains unclear. The objective of this meta‐analysis was to compare the effects of VA dual therapy with BQT for H. pylori eradication. Methods: A comprehensive search of the literature was conducted from the beginning to September 2023, utilizing PubMed, Embase, the Cochrane Library and Web of Science database. A random‐effects model was used to perform a meta‐analysis to determine the pooled relative risk (RR) with 95% confidence intervals (CIs). Moreover, trial sequential analysis (TSA) was conducted to evaluate the conclusiveness of the H. pylori eradication rate. Results: Six randomized controlled trials (RCTs) with 1233 patients were included. The VA therapy has similar eradication rate (ITT analysis: 87% vs. 85.7%, RR = 1.01, 95% CI: 0.93–1.09, p = 0.84; PP analysis: 92.5% vs. 93.2%, RR = 1.00, 95% CI: 0.94–1.06, p = 0.97) and compliance (RR = 1.01, 95% CI: 0.99–1.03, p = 0.32) compared to BQT. The VA therapy group had a significantly lower incidence of total adverse events than the BQT group (16.3% vs. 40.0%, RR = 0.45, 95% CI: 0.37–0.55, p < 0.00001). The TSA result showed that the effect was conclusive. Conclusions: Current evidence indicated that VA therapy is just as successful as BQT in eliminating H. pylori, yet it has fewer adverse events and similar compliance. [ABSTRACT FROM AUTHOR]