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Objective: To observe the clinical efficacy of Yunnan Baiyao (云南白药, YNBY) combined with antibiotics in treating Helicobacter pylori (HP) related duodenal ulcer (DU). Methods: Eighty-two HP positive DU patients were randomly divided into two groups: Treated group (44 cases) used YNBY plus amoxicillin and metronidazole; control group (38 cases) used de-nol plus amoxicillin and metronidazole). Results: After a 2-week treatment course, the effect of epigastric pain relief was 68.3% in treated group, and 44.4% in control group, the difference between them was significant (P<0.05). Marked effect in acid regurgitation and belching relief was observed in both groups. The rate of DU healing in treated and control group was respectively 88.6% and 89.5%; the clearance of HP 84.1% and 89.5%; and the side-effects 4.5% and 13.5%, with insignificant difference between these two groups. Conclusion: YNBY combined with antibiotics in treating DU, and clearance of HP is an economic, safe and effective therapy.