Objective To explore the application value of a new dual seven day regimen of vonolaxan combined with high-dose Amoxicillin in the treatment of Helicobacter pylori (H.pylori)infection. Methods A total of 260 patients with H. pylori infection diagnosed in Dongguan Songshan Lake Tungwah Hospital from June 2021 to June 2022 were selected and randomly divided into a study group of 130 cases and a control group of 130 cases. The study group received the new 7-day regimen of vonolaxan combined with high-dose Amoxicillin, while the control group received the two-week regimen of Rabeprazole combined with high-dose Amoxicillin. Repeat the 13C urea breath test at least 4 weeks after treatment, and a negative result indicates successful eradication. Compare the general information, incidence of adverse reactions, eradication rate of H. pylori,treatment costs, and medication compliance between the two groups of patients. Intention to treat (ITT) and per protocol (PP) were used to analyze the eradication effects of H. pylori with different regimens, respectively. Results A total of 221 out of 260 patients completed treatment, follow-up, and review, including 109 in the study group and 122 in the control group. There was no statistically significant difference in general information and incidence of adverse reactions between the two groups of patients (P>0.05). ITT and PP analysis showed that the eradication rates of H. pylori in the study group and control group were 72.6%, 90.0%, and 74.1%, 91.5%, respectively,with no statistically significant difference (P>0.05). Comparison of treatment costs, the research group's plan has lower prices and better drug economic benefits. In terms of medication compliance, the study group was significantly higher than the control group (P<0.05). Conclusion The new dual seven day regimen of vonolaxan combined with high-dose Amoxicillin is effective in the treatment of H. pylori infection, with few adverse reactions, low cost and high compliance of patients. It is expected to become a new scheme and option for the eradication of H. pylori infection in the future