With the increasing prevalence of antibiotic resistance, the clinical efficacy of conventional 7-day triple therapy for Helicobacter pylori eradication has been substantially diminished. However, the efficacy and safety of a 7-day triple regimen based on amoxicillin and tetracycline warrant further investigation. This retrospective study was designed to compare the efficacy and safety of a 7-day triple therapy based on amoxicillin and tetracycline combination versus the standard 14-day high-dose dual therapy for H. pylori infection. Data on therapies for H. pylori eradication were extracted between January 2023 and October 2025 at Qilu Hospital of Shandong University. Two regimens were compared based on 1:3 propensity score matching: 7-day triple therapy (vonoprazan 20 mg twice daily, amoxicillin 1000 mg twice daily, and tetracycline 500 mg four times daily) and 14-day high-dose dual therapy (vonoprazan 20 mg twice daily and amoxicillin 1000 mg three times daily). Eradication rates and incidence of adverse events were assessed.