Background: Helicobacter pylori (H. pylori) associated peptic ulcer represents a therapeutic challenge with almost no regimen having achieved 100% eradication due to the emergence of antibiotic resistance. H. pylori virulence genes not only contribute in its pathogenesis but also have an influence on antibiotic resistance. Hence, the study of virulence genes effect on the acquisition of drug resistance may be an avenue to explore how to improve H. pylori eradication rates. Objectives: To estimate the prevalence of H. pylori cytotoxin-associated gene A (CagA) positive genotype among peptic ulcer(PU) patients, and to evaluate if there is an association between CagA virulence gene status and antibiotic resistance patterns in H. pylori strains. Methodology: Gastric biopsy specimens were collected from 54 enrolled patients with suspected peptic ulcer disease. Eighteen gastric biopsy specimens yielded H. pylori growth which were confirmed microscopically and by biochemical traits. Antimicrobial susceptibility patterns of H. pylori isolates were determined by disc diffusion and agar dilution methods. CagA was determined using PCR. Results: H. pylori CagA positive isolates were more significantly presented among peptic ulcer patients 13/18 (72.2%) compared to CagA negative isolates 5/18 (27.8%). High rates of antibiotic resistance against the first-line regimen of H. pylori associated PU were revealed with resistance rates of 100%, 61.1%, and 50% to metronidazole, amoxicillin and clarithromycin respectively, however (14/18; 87.8%) of H. pylori isolates were susceptible to ciprofloxacin and tetracycline. H. pylori CagA negative strains were associated with high levels of resistance to ciprofloxacin, clarithromycin, amoxicillin and tetracycline compared to CagA positive isolates. Conclusion: this work elucidated the high prevalence of H. pylori CagA positive genotype among Egyptian patients. The high level of resistance against the first line regimen of H. pylori associated peptic ulcer is alarming. Ciprofloxacin and tetracycline, both drugs can be the best choice in treating peptic ulcer patients. Absence of CagA gene in H. pylori was associated with high degrees of resistance and the presence of CagA gene be a predictor marker for H. pylori successful eradication