AIM: To evaluate the clinical efficacy of amoxicillin from volume-based procurement (VBP) and potassium amoxicillin clavulanate in the eradication of helicobacter pylori (Hp) infection, providing basis for the selection of treatment programs. METHODS: Data from the patients who received Hp eradication therapy from May 2021 to May 2022 were recruited from the rational drug use management system. The data from the patients treated by amoxicillin (amoxicillin 1.0 g bid + bismuth potassium citrate 220 mg bid + esomeprazole 20 mg bid + clarithromycin 0.5 g bid, for 14 days) and potassium amoxicillin clavulanate (potassium amoxicillin clavulanate 0.914 g bid + bismuth potassium citrate 220 mg bid + esomeprazole 20 mg bid + clarithromycin 0.5 g bid, for 14 days) were selected and compared. RESULTS: A total of 171 cases were collected in the group treated by Amoxicillin program, and the eradication rate was 87.8% (150/171). A total of 69 cases were collected in the group of potassium amoxicillin clavulanate, and the eradication rate was 76.8% (53/69). There was no significant difference in baseline data between the two groups (P>0.05). There was a significant difference in clinical efficacy between the two groups (P<0.05). In addition, the cost-effectiveness ratio (C/E) of the Amoxicillin treatment program was lower than that of the potassium amoxicillin clavulanate program CONCLUSION: The clinical efficacy of VBP Amoxicillin program in eradicating Hp infection is better than that of the potassium amoxicillin clavulanate program, which is worthy of clinical recommendation.