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This study aimed to compare the effectiveness of vonoprazan-amoxicillin based dual therapy with that of quadruple therapy as second-line treatments, while also investigating potential clinical predictors of therapeutic success. From January 2023 to June 2025, we retrospectively analyzed clinical data from\n                    <jats:italic>H. pylori<\/jats:italic>\n                    -infected patients who received second-line treatment with either: vonoprazan-amoxicillin dual therapy (VA) or VA based quadruple therapy (VAMB; vonoprazan, amoxicillin, minocycline, and colloidal bismuth pectin). The eradication status was evaluated by\n                    <jats:sup>13\/14<\/jats:sup>\n                    C\u00adurease breath test four weeks after treatment completion. Adverse events and medication compliance were systematically documented during follow-up. The study included 241 patients, with 107 receiving VA dual therapy and 134 undergoing VAMB quadruple therapy. Eradication rates were comparable between groups: 90.7% (VA) versus 92.5% (VAMB) by modified intention-to-treat (mITT) analysis, and 91.4% versus 93.7% by per-protocol (PP) analysis (all\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.05). Notably, the VA regimen demonstrated significantly fewer adverse events (8.4%\n                    <jats:italic>vs<\/jats:italic>\n                    17.9%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.033). Both treatment arms maintained excellent medication adherence. Compared to the vonoprazan-amoxicillin-minocycline-bismuth (VAMB) quadruple regimen, vonoprazan-amoxicillin (VA) dual therapy achieved comparable eradication efficacy with a more favorable safety profile in second-line\n                    <jats:italic>H. pylori<\/jats:italic>\n                    treatment, representing a simplified yet effective rescue therapy option.\n                  <\/jats:p>","DOI":"10.1007\/s10238-025-02037-8","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T10:23:13Z","timestamp":1768904593000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative effectiveness and safety of vonoprazan\/amoxicillin-based dual therapy versus quadruple therapy as second-line treatment for Helicobacter pylori Infection: a retrospective cohort study"],"prefix":"10.1007","volume":"26","author":[{"given":"Ying-Ying","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ni","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Tuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Mei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Zhen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6300-1460","authenticated-orcid":false,"given":"Pei-Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"issue":"12","key":"2037_CR1","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1056\/NEJMcp1710945","volume":"380","author":"SE Crowe","year":"2019","unstructured":"Crowe SE. 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