Background: The main purpose of the current study was to determine the effect of treating helicobacter pylori (HP) infection on seizure frequency in patients with refractory epilepsy.Methods: A small sample of adult patients above 18 years of age with a diagnosis of refractory epilepsy was studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, from January 2009 through June 2011. If and when urea breath test result was positive, an upper endoscopy with multiple gastric biopsies was requested. Rapid urease test and histopathology examination were performed. For patients with confirmed HP infection, treatment with clarithromycin, amoxicillin and omeprazole was ordered for two weeks. Seizure frequency was recorded before and after HP treatment.Results: Nine patients were recruited. Using Wilcoxon signed ranks test, seizure frequency did not differ significantly after HP treatment compared to the period before treatment (P = 0.6).Conclusion: Treating HP infection in patients with refractory epilepsy did not significantly change the seizure frequency.