Background: Helicobacter pylori [H. Pylori] infection is a major risk factor for the development of gastric cancer. Gastric cancer witnessed a significant increase in recent decades. Thus, eradication of H. Pylori could reduce the incidence of gastric cancer. However, the standard treatment is not yet determined. 
Aim of the Work: To evaluate the efficacy of Vonoprazan [VPZ]-based regimen compared-with proton pump inhibitors [PPI]-based regimen for H. pylori eradication therapy.
Patients and Methods: This study included 150 patients with gastro-intestinal symptoms and H. Pylori positive test. They were divided into equal three groups according to treatment regimen. The first group [I] received PPI-based regiment [triple therapy; Clarithromycin 500 mg, amoxicillin 1gm, and PPI 40 mg] twice daily for two weeks. The second group [II] received vonoprazan-based regiment [triple therapy; Clarithromycin 500 mg, amoxicillin 1 gm, and vonoprazan 20 mg] twice daily for two weeks. The third group also for vonoprazan-based regimen [dual therapy; [amoxicillin 1gm –vonoprazan 20 mg] twice daily for two weeks.
 Results: The analysis indicates that the eradication rate of H. Pylori was 88% in group I, 92% in group II and 84% in group III. There was no significant difference between the three studied groups regarding eradication rate. In addition, groups were comparable regarding patient demographics except younger age of the first group than the second and third groups. Otherwise, no significant associations [differences] between groups were reported.
Conclusion: Vonoprazan triple therapy is superior to PPI- triple therapy. The dual vonoprazan-therapy is highly recommended in case of clarithromycin resistant patients. Otherwise, the triple vonoprazan therapy is recommended.