Background: Helicobacter pylori is one of the most common, medically prominent infection worldwide and one of the major causative factor of peptic ulcer disease. So, eradication of H. pylori is effective in healing ulcers, reducing the ulcer recurrence and eliminating the need for maintenance therapy. Objective: The aim of the work was to compare between the efficacy of traditional triple therapy and Moxifloxacin-based triple therapy in treatment of H. pylori infection and to evaluate the efficacy of moxifloxacin-based regimens as a rescue regimen for H. pylori eradication in resistant patients. Patients and methods: This study was carried out on 100 Helicobacter pylori (H. pylori)-infected patients (within the period between septemper, 2018 to May, 2019) who were enrolled from Hepatology, Gastroenterology & Tropical Medicine Department, Al Azhar University Hospitals (El-Hussein and BAB El-Shaarea). Results: Helicobacter pylori eradication results in group III as evaluated by monoclonal H. Pylori stool Ag, 6 weeks post therapeutic regimens reported that eradication rate was 76.9% (20 patients). Regarding post treatment clinical data in group III, 42.3% of patients remained having symptoms and 57.7% had acheived symptomatic improvement. Also, the best results were recorded for H.pylori eradication (90%) in group II who received moxifloxacin based triple therapy compared to group I (with eradication rate 62.9%) who received traditional triple therapy regimen. Thus the better results (76.9%) were achieved in group III (resistant patients from group I). Conclusion: The present results could state that moxifloxacin can overcome traditional triple therapy resistance.