Background: Association between Helicobacter pylori (HP) infection and migraine and the effect of HP eradication on relief of migraine headache have been studied but the results are controversial. Objectives: To evaluate the effect of HP eradication in treatment of patients affected by migraine. Materials and Methods: Eighty consecutive HP infected patients affected by migraine without aura were enrolled in this clinical trial. They have referred to an endoscopy clinic for work-up of HP infection from October 2013 to November 2014. Patients were randomly assigned in 2 groups using 2 different regimens; Group A: migraine treatment and a 14-day triple therapy for HP infection and Group B: migraine treatment without HP eradication. The mean duration (hour), headache severity (MIDAS) and the frequency (per month) of clinical headache attacks were calculated upon enrollment in the study and at 6 months and 12 months after treatment. All data were analyzed using SPSS version 16. Comparison of categorical variables across the groups was performed using Chi-square test. Results: In group A, HP infection was eradicated in 34 of 40 patients (85%). After treatment in eradicated patients compared with the control group there was significant decrease in severity and frequency (but not in duration) of the migraine attacks at 6 months (p<0.001) and significant decrease in intensity, frequency and duration of the migraine attacks at 12 months (p<0.001). Conclusion: HP should be considered and examined in migranous patients and eradication treatment can be beneficial for relief of clinical attacks.