Objective：To study and compare the different curative effects on Barrett’s esophagus（BE） by using esomeprazole magnesium，omeprazole and lansoprazole as the basic therapeutic regimen respectively. Methods：Totally 87 patients were randomly selected and divided into three groups. Esomeprazole magnesium，omeprazole and lansoprazole were given to the three groups respectively. Changes of BE before and after the treatment（1-5 weeks） and during the long-term maintenance treatment（12-24 months） were carefully observed. Results：Data indicated that there were significantly statistical differences among the three groups；esomeprazole magnesium group displayed more positive results than omeprazole group and lansoprazole group in the control of helicobacter pylori（Hp） infection and alleviation of gastroesophageal reflux disease（GERD） and BE symptoms（P=0.019，P=0.007）. Concerning the direct treatment effect on BE，evaluation indicators including metaplasia length reduction rate（P=0.028 2），metaplasia area reduction rate（P=0.022 6），squamous epithelium detection rate（P=0.001） and mixed epithelium detection rate（P=0.003） were better in esomeprazole magnesium group than in omeprazole group and lansoprazole group. Concerning the prevention of BE，there was no statistical difference among esomeprazole magnesium group，omeprazole group and lansoprazole group in number of cases with metaplasia aggravation after the treatment（P=0.483）. Adverse reaction detection showed that esomeprazole magnesium group had lower incidence rate than omeprazole group and lansoprazole group（P=0.013），indicating that the former treatment was much safer than the latter ones. Conclusion：Therapy with esomeprazole magnesium is much safer and more dependable with lower adverse effects. It is able to control the Hp infection more effectively，inhibit the secretion of gastric acid，alleviate or eliminate the erosion of GERD on the mucous membrane epithelium of esophagus，promote the esophageal epithelial cell proliferation，which，to some extent，contributes to the remedy of the pathological tissues and restrain BE from developing into esophageal adenocarcinoma.