Background and Study Aims. The association between Helicobacter pylori (H. pylori) and chronic spontaneous urticaria (CSU) remains controversial. This study explored the role of H. pylori in CSU among different virulent genotypes patients. Patients and Methods. Patients infected by H. pylori were sorted into two groups as group A (with CSU) and group B (without CSU). The tissue materials were taken via endoscopy for polymerase chain reaction study to determine virulence factors. After H. pylori eradication therapy, the eradication rate and response of urticaria were evaluated by using C 13 -UBT and a three-point scale (complete remission, partial remission, or no improvement). Results. The results were comparable between patients of groups A and B in terms of H. pylori infection rates and eradication rate. Longitudinal follow-up of 23.5 months showed complete remission of urticaria in 63.6% but no improvement in 36.4% of the patients after H. pylori eradication. H. pylori infected patients with different virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin gene A signal region and middle region have similar remission rates for CSU. Conclusions. Current study suggests that H. pylori may play a role in the development and disease course of CSU but may be irrelevant to different virulent genotypes