Background: Helicobacter pylori (H. pylori) is a gram-negative, micro-aerophilic, curved rod that causes a transmissible bacterial infection of the gastric mucosal surface and affect about one half of the world’s population. It induces chronic gastritis in all infected individuals, but only induces clinical diseases in 10-20% of them. This may be related to differences in genetic susceptibility of the host, environmental factors, and genetic diversity of H. pylori. Aim: This study was conducted to identify the frequency of the genetic virulence factors (cagA, vacA and babA2) of H. pylori and their possible association with gastroduodenal diseases. Methods: The study was conducted on 70 adult patients with upper gastrointestinal complaints. All patients were subjected to full history taking, clinical examination, gastroduodenoscopy. Four antral biopsies were taken for genotyping by PCR, histopathological examination and culture. Results: All the patients (100%) had chronic active H. pylori gastritis by histopathological examination. The most frequent H. pylori genotype was cagA (67.8%) followed by vacA s1a (61%) and vacA m2 (61%), while the least frequent was babA2 (18.6%). CagA was associated with vacA s1a in (83.3%) with statistical significance. Most patients with cagA positive isolates (77.8%) had no heart burn with statistical significance which may support the protective role of cagA against GERD. There was no significant difference between genotypes distribution as regards culture positive and culture negative H. pylori strains. CagA, vacA s1a and vacA m2 had the highest prevalence in patients with PUD, gastritis and duodenitis while babA2 had the least prevalence. Although in patients with PUD and NUD the prevalence of cagA was (65.1%, 75%) and vacA s1 was (62.8%, 56.3%) respectively, the association between these H. pylori genotypes and PUD did not reach a level of statistical significance. Conclusion: None of H. pylori genetic virulence factors individually can accurately predict clinical outcome and one has to recognize the importance of the bacteria-host interaction in the final outcome.