Background: Clarithromycin is one of the most common drugs recommended as first-line eradication therapy for H. pylori infection but the prevalence of clarithromycin resistant H. pylori is increasing. Clarithromycin-resistance is associated with point mutations in the 23S rRNA gene. Objective: Detecting the frequency of H. pylori clarithromycin resistance and demonstrating clarithromycin resistant genotypes A2142G and A2143G. Methodology: This study included 123 patients during upper gastroduodenoscopy in the Endoscopy Units of Zagazig University Hospitals. Three gastric biopsies were obtained from each patient. H. pylori infection was detected by rapid urease test, histopathology, and PCR. The biopsy was considered H. pylori positive if both rapid urease test and histopathology were positive. Clarithromycin resistance was assessed by Polymerase chain reaction-amplification and restriction fragment length polymorphism (PCR-RFLP). Results: Out of 123 patients, 71 patient were infected with H. pylori. Clarithromycin resistance was detected in 47 of 71 positive H. pylori strains (66.19 %), the A2142G point mutation was detected in 37 cases (52.11%) , A2143G in 10 cases (14.08 %) while dual point mutations were observed in 2 cases (2.81%). In conclusion: High prevalence of clarithromycin resistant H. pylori among Egyptian patients .The A2142G is the most frequent detected point mutations involved in clarithromycin resistance in our country.