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Background Helicobacter pylori (H. pylori) infection and eradication are still major health concerns. One week of triple therapy with a potassium-competitive acid blocker has been recommended in some Asian countries as an alternative first-line treatment of H. pylori infection. This meta-analysis aims to identify the non-inferiority of Vonoprazan-based triple therapy to standard proton pump inhibitor (PPI)-based therapy in the treatment of H. pylori infection and evaluate the adverse outcomes in both groups.Methods Randomized controlled trials were eligible for inclusion if enrolled participants were diagnosed as positive for H. pylori on the basis of one or more confirmatory tests. Participants had to be naıve to H. pylori eradication treatment. Databases were searched for articles published until June 2024. The reference lists of each of the studies were also reviewed. The main efficacy outcome was H. pylori eradication and safety outcomes include the rate of adverse events.Results Pooled eradication rates in Vonoprazan-based Triple therapy versus PPI-based triple therapy were 89.5% and 78.9% respectively (Odds Ratio [OR] 0.41; 95% Confidence Interval [CI], 0.22 to 0.77; p=0.005) in the Intention-to-treat (ITT) analysis ( IDDF2026-ABS-0456 Figure 1. Eradication of Vonoprazan-based triple therapy versus PPI-based triple therapy ITT analysis) and 92.3% and 81.6% respectively (Odds Ratio [OR] 0.37; 95% Confidence Interval [CI], 0.21 to 0.66; p=0.0008) in the per protocol (PP) analysis (IDDF2026-ABS-0456 Figure 2. Eradication of Vonoprazan-based triple therapy versus PPI-based triple therapy: PP analysis). Subgroup analysis revealed superiority of Vonoprazan-based triple therapy with values of 93.2% and 81.3% respectively (Odds Ratio [OR] 0.31; 95% Confidence Interval [CI], 0.18 to 0.53; p=<0.0001) (IDDF2026-ABS-0456 Figure 3. Eradication of Vonoprazan-based triple-therapy versus PPI-based triple-therapy in subgroup analysis).Analysis of adverse events in Vonoprazan-based Triple therapy versus PPI-based triple therapy were 35.3% and 38.9% respectively (Odds Ratio [OR] 0.86; 95% Confidence Interval [CI], 0.71 to 1.04; p=0.13). Most common adverse events included diarrhea, dysgeusia and bloatedness (IDDF2026-ABS-0456 Figure 4. Treatment-related adverse events in Vonoprazan-based triple therapy versus PPI-based triple therapy).Conclusions H. pylori eradication in Vonoprazan-based Triple therapy in a per-protocol subgroup analysis demonstrated superiority to PPI-based triple therapy. Eradication rates in Vonoprazan-based Triple therapy versus PPI-based triple therapy in the Intention-to-treat and per-protocol analyses demonstrated comparable results; however, there was significant heterogeneity.Most common adverse events include diarrhea, dysgeusia and bloating/abdominal fullness. The difference in incidence of total adverse events between Vonoprazan-based Triple therapy versus PPI-based triple therapy across the included RCTs is not significant. Abstract IDDF2026-ABS-0456 Figure 1Abstract IDDF2026-ABS-0456 Figure 2Abstract IDDF2026-ABS-0456 Figure 3Abstract IDDF2026-ABS-0456 Figure 4