Aims To investigate the prevalence of Helicobacter pylori infection in Lebanon and the association between virulence factors (cytotoxin-associated gene A and vacuolating cytotoxin gene A), ABO blood groups, and disease phenotype. Methods One hundred and thirty symptomatic patients with H. pylori-associated endoscopic findings and 104 healthy male donors (age range 18–55) were evaluated. Both, patients and donors underwent ABO blood typing and Western blot for cytotoxin-associated gene A and vacuolating cytotoxin gene A. Results The prevalence of H. pylori infection in healthy donors is 68.3%. Type I (cytotoxin-associated gene A- and vacuolating cytotoxin gene A-positive) was the predominant phenotype in all groups, though significantly less common in the asymptomatic population (46.5%) than in patients with benign disease (71.4%, p < 0.01) or malignancy (71.6%, p < 0.05). Type II (cytotoxin-associated gene A- and vacuolating cytotoxin gene A-negative) and vacuolating cytotoxin gene A-only strains were more common in the asymptomatic cohort. Overall, 35.2% of asymptomatic individuals and 10.8% of patients with benign disease were cytotoxin-associated gene A-negative ( p < 0.01). There was no significant association between immunoserotypes, ABO groups or benign gastroduodenal disease. All gastric malignancies (lymphoma and adenocarcinoma) were cytotoxin-associated gene A-positive but this was not significantly different from patients with benign disease. We found a higher prevalence of blood group A in patients with gastric malignancy than in the general population [47.6% versus 25%, p = 0.037; RR = 2.73 (1.04–7.16; 95% CI)]. Conclusions The seroprevalence of H. pylori is moderately high in Lebanon. Phenotypic classification identifies a higher prevalence of Type I in symptomatic patients. A significant relationship between infection with a cytotoxin-associated gene A-positive strain in blood type A patients and the risk of gastric malignancy was noted.