AIM To evaluate the effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality. METHODS Forty-eight patients diagnosed with gastric ulcer between June 2014 and February 2016 were randomly alloc at e d t o t he c ombinat ion t he r apy gr oup or monotherapy group. The former received hydrotalcite combined with esomeprazole, and the latter received esomeprazole alone, for 8 wk. Twenty-four healthy volunteers were recruited and acted as the healthy control group. Endoscopic ulcer healing was observed using white light endoscopy and narrow band imaging magnifying endoscopy. The composition of collagen fibers, amount of collagen deposition, expression of factor Ⅷ and TGF-β1, and hydroxyproline content were analyzed by Masson staining, immunohistochemistry, immunofluorescent imaging and ELISA. RESULTS Following treatment, changes in the gastric microvascular network were statistically different between the combination therapy group and the monotherapy group(P < 0.05). There were significant differences(P < 0.05) in collagen deposition, expression level of Factor Ⅷ and TGF-β1, and hydroxyproline content in the two treatment groups compared with the healthy control group. These parameters in the combination therapy group were significantly higher than in the monotherapy group(P < 0.05). The ratio of collagen?Ⅰ?to collagen Ⅲ was statistically different among the three groups, and was significantly higher in the combination therapy group than in the monotherapy group(P < 0.05). CONCLUSION Hydrotalcite combined with esomeprazole is superior to esomeprazole alone in improving gastric ulcer healing quality in terms of improving microvascular morphology, degree of structure maturity and function of regenerated mucosa. AIM To evaluate the effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality. METHODS Forty-eight patients diagnosed with gastric ulcer between June 2014 and February 2016 were randomly allocated at edtot he c ombinat ion t he r apy gr oup or monotherapy group. The former received hydrotalcite combined with esomeprazole, and the latter received esomeprazole alone, for 8 wk. Twenty-four healthy volunteers were recruited and acted as the healthy control group. Endoscopic ulcer healing was observed using white light endoscopy and narrow band imaging magnifying endoscopy. The composition of collagen fibers, amount of collagen deposition, expression of factor VIII and TGF-β1, and hydroxyproline content were analyzed by Masson staining, immunohistochemistry, immunofluorescent imaging and ELISA. RESULTS Following treatment, changes in the gastric microvascular network were statistically significant the combination therapy group and the monotherapy group (P <0. 05). There were significant differences (P <0.05) in collagen deposition, expression level of Factor VIII and TGF-β1, and hydroxyproline content in the two treatment groups compared with the healthy control group. These parameters in the combination therapy group were significantly The ratio of collagen? Ⅰ? to collagen Ⅲ was statistically different among the three groups, and was significantly higher in the combination therapy group than in the monotherapy group (P <0.05). CONCLUSION Hydrotalcite combined with esomeprazole is superior to esomeprazole alone in improving gastric ulcer healing quality in terms of improving microvascular morphology, degree of structure maturity and function of regenerated mucosa.