Background: Worldwide about 12-15% of population complains of migraine at some point of their lives. Gastrointestinal disorders and infections including Helicobacter pylori (H. Pylori) have been the focus of many researches to delineate their relationship with migraine headache Objectives: To assess the coexistence of H. pylori and migraine headache and to assess the effect of H. pylori eradication on migraine impact among Egyptian patients. Methodology: In this case control study, eighty migraine patients and eighty age and sex matched healthy controls were enrolled. Migraine impact on patient’s life was assessed on initial case evaluation by Migraine Disability Assessment Test (MIDAS1). H. pylori stool antigen test was done for all participants. H. pylori infected cases received levofloxacin based triple therapy and symptomatic control group received first line clarithromycin based therapy for 2 weeks. H. pylori stool antigen test was repeated 4 weeks after treatment regimen was completed. Reassessment of all cases by MIDAS2 was also done after 3 months of completing therapy. Results: The predominance of female gender was reported in migraine patients. Case group had statistically significant more GIT manifestations as heart burn, epigastric pain and GIT bleeding compared with control volunteers. There was significantly higher prevalence of H. pylori infection in patient group than controls (P <0.05). H. pylori eradication rate was significantly higher in levofloxacin based regimen than clarithromycin based one (P < 0.05). H. pylori eradication caused statistically significant reduction of MIDAS score after treatment (P<0.001).Conclusions: The frequency and severity of migraine headache may be postulated to H. Pylori infection. Eradication of H. pylori gastric infection induces marked clinical improvement of migraine. Levofloxacin based therapy is more efficient than clarithromycin based therapy in H. pylori eradication in Egyptian patients.