Background: Metronidazole is one of the antimicrobial drugs that can be used in combination with other drugs for eradication of Helicobacter pylori (H. pylori).Unfortunately, metronidazole resistance in H. plori is an increasing health problem which may be attributed to inactivation of many genes as rdx A gene. Objective: To determine the frequency of rdx A deletion mutation in H. pylori detected in infected patients attending at the Gastroenterology Unit, Zagazig University Hospitals. Methodology: Two gastric biopsies were taken from each enrolled patient by endoscopy. H.pylori detection was done by rapid urease test and polymerase chain reaction (PCR) amplification of 16S rRNA gene. Deletion mutation in rdx A gene was detected by conventional PCR. Results: Out of 134 doubled gastric biopsies obtained from 134 patients, 52.2% were positive for H. pylori. Epigastric pain, vomiting and gastritis were significantly associated with detection of H. pylori infection (p˂ 0.05). Deletion mutation of rdx A gene was detected in 28.6% of H. pylori positive specimens obtained from infected patients. Conclusion: Deletion mutation of rdx A gene is a frequent determinant of rdx A inactivation conferring metronidazole resistance among H. pylori.