OBJECTIVE：To observe the efficacy and safety of proton pump inhibitors combined with Compound digestive enzyme tablet in the treatment of epigastric pain syndrome with abdominal distension. METHODS： 156 patients with epigastric pain syndrome with abdominal distension were randomly divided into control group （75 cases） and observation group （81 cases）. Control group was given 40 mg Esomeprazole enteric-coated tablet for once half an hour before breakfast； observation group was additionally given 243.6 mg Compound digestive enzyme tablet immediately after meal， 3 times a day. The treatment course for both groups was 2 weeks. Clinical efficacy， clinical symptom score， pepsinogenⅠ（PGⅠ）， pepsinogenⅡ（PGⅡ），2，4 h postprandial gastric emptying rate before and after treatment， and incidence of adverse reactions in 2 groups were observed. RESULTS： The total effective rate in observation group was significantly higher than control group， the difference was statistically significant （P＜0.05）. There was no significant difference in the incidence of adverse reactions between 2 groups （P＞0.05）. Before treatment， there were no significant differences in the clinical symptom score， PGⅠ， PGⅡ and 2， 4 h postprandial gastric emptying rate （P＞0.05）. After treatment， clinical symptom score in 2 groups were significantly lower than before， and observation group was lower than control group； PGⅠ and PGⅡ in observation group were significantly higher than before and control group， the differences were statistically significant（P＜0.05）； and there were no significant differences in the 2， 4 h postprandial gastric emptying rate between 2 groups and PGⅠ and PGⅡ in control group before and after treatment （P＞0.05）. CONCLUSIONS： The efficacy of proton pump inhibitors combined with Compound digestive enzyme tablet is superior to the proton pump inhibitors in the treatment of epigastric pain syndrome with abdominal distension， with similar safety.