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: 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 September, 2018 to May 2019) who were enrolled from Gastroenterology, Liver and Infectious Disease Department Al-Azhar University Hospitals (Al-Hussein and BAB Al-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 achieved symptomatic improvement. The best results for H.pylori eradication 90% was in group II who received Moxifloxacin based triple therapy, compared with group I eradication rate 62.9% who received traditional triple therapy regimen, and better results 76.9% in group III (resistant patients from group I). Conclusion: Moxifloxacin can overcome traditional triple therapy resistance.