- Background. Some patients with chronic spontaneous urticaria (CU) are resistant to conventional doses of antihistamine (AH) medications. Some research groups have reported an association between CU and Helicobacter pylori infection. Aim. To determine whether H. pylori eradication can reverse AH resistance in CU. Methods. We retrospectively reviewed cases of patients with CU, and recorded their Urticaria Activity Score (UAS) and results of a (13) C-urea breath test ((13) C-UBT) for H. pylori infection. Patients without improvement in CU despite a full 8 weeks of AH treatment at four times the initial dose comprised the resistant CU group, while the patients who did respond comprised the responsive CU group. Patients with resistant CU and a positive (13) C-UBT (n = 46) were offered a 14-day treatment with amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily and omeprazole 20 mg twice daily. The effect of H. pylori eradication on CU was evaluated by the UAS, measured at baseline and at 8, 16, and 28 weeks after triple therapy. Results. Of the 46 patients with resistant CU, 29 (63%) had a positive (13) C-UBT result. Treatment eradicated H. pylori in 18 of the 29 patients (subgroup A), and 11 patients refused the triple therapy (subgroup B). The remaining 17 patients had a negative (13) C-UBT result, (subgroup C). In subgroup A, baseline UAS reduced from 5.29 ± 0.94 to 3.62 ± 0.96 (P = 0.03) at week 8; to 1.43 ± 0.41 (P < 0.001) at week 16, and to 1.17 ± 0.32 (P = 0.04) at week 28. Five of the patients (27.8%) in this group were completely free of symptoms at week 28, whereas none of the untreated patients achieved complete remission. Conclusion. Some patients with resistant CU might benefit from H. pylori eradication.