Abstract： Objective： To observe the clinical effect of Puqiao Yigong tang combined with routine quadruple therapy containing bismuth agent for Helicobacter pylori(Hp)-associated gastric ulcer with spleen-stomach deficiency cold syndrome. Methods：A total of 60 cases of patients who met inclusion criteria and exclusion criteria in the Digestive Department were selected，and divided into two groups according to the random number table method，30 cases in each group. The control group was treated with quadruple therapy for 14 days，and the sequential treatment of oral administration of esomeprazole magnesium enteric- coated tablets for 6 weeks. The observation group was additionally given Puqiao Yigong tang based on the treatment of the control group. Both groups were treated for 8 weeks， and the curative effect was evaluated. After treatment，the indexes of clinical effect and safety indexes were observed. Patients who had Hp cured and eradicated under gastroscopy were followed up for four months. The long-term curative effect was evaluated. Results：After treatment，the total effective rate was 93.33% in the observation group， and 90.00% in the control group； there was no significant difference being found in the comparison of Hp infection between the two groups(P＞0.05). Four months after treatment，the recurrence rate was 10.71% in the observation group，and 37.04% in the control group，the difference being significant(P＜ 0.05). The healing rate of gastric ulcer was 46.67% in the observation group， and 33.33% in the control group； the total effective rate was 93.33% in the observation group，and 76.67% in the control group，the difference being significant(P＜ 0.05). Four months after treatment，with the recurrence rate being 7.14%，there was 1 recurrence case in the 14 patients of the observation group that recovered from ulcer； with the recurrence rate being 40.00%，there were 4 recurrence cases in the 10 patients of the control group that recovered； the comparison of the recurrence of ulcer between the two groups showed significance in the difference(P＜0.05). After treatment，when compared the positive rate of immunohistochemical expressions of cyclooxygenase- 2(COX- 2)， nuclear- factor kappa B p65(NF- κBp65)， and trefoil factor(TFF3)， there was significance in differences(P＜0.05). In the two groups， each Chinese medicine symptom score was decreased when compared with that before treatment， differences being significant(P＜0.05). After treatment， when compared symptom scores of stomach duct pain，relief of pain due to food intake，lack of strength in limbs，cold limbs and fear of cold，torpid intake and lack of appetite between the two groups，there was significance in differences(P＜0.05). During the study，there was no obvious abnormality in safety indexes of the two groups，and no adverse reactions； blood routine，urine routine， stool routine，the heart，liver，and kidney function，and electrocardiogram examination in both groups were normal before and after treatment. Conclusion： In the treatment of Hp- associated gastric ulcer with spleen- stomach deficiency cold syndrome，the comparison of the eradication rate of Hp showed no obvious difference between the therapy of Puqiao Yigong tang combined with routine quadruple therapy containing bismuth agent and simple quadruple therapy containing bismuth agent. But the combination therapy can decrease the long- term recurrence rate of Hp infection and gastric ulcer，improve Chinese symptoms of the disease with various degrees， increase the healing rate of gastric ulcer， and effectively reduce expression levels of tumor risk factors including COX-2，NF-κBp65，and TFF3，with high clinical safety.