Abstract: ObjectiveTo evaluate the effect of proton pump inhibitors (PPIs) therapy on severe acute pancreatitis (SAP) patients. MethodsForty five patients with SAP recruited in our center from October 2015 to October 2016, were randomly assigned into two groups: convention group (C group, n=21) and convention+esomeprazole group (C+E group, n=24). C+E group received esomeprazole 40 mg/d intravenously for 1 week, whereas C group only received baseline treatment. Serum C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and procalcitonin (PCT) were detected by ELISA on the first day (baseline) and the seventh day. Acute physiology and chronic health evaluation Ⅱ scores (APACHE Ⅱ), systemic inflammatory response syndrome scores (SIRS) and modified Marshall scoring system （Marshall） were obtained at 1 d (baseline), 3 d and 7 d. Upper gastrointestinal manifestation (peptic ulcer) and gastric pH were detected by endoscopic examination at 7 d. Fecal occult blood test was performed at 7 d. ResultsNo significant difference was found in CRP, IL-6, IL-8, TNF-α and PCT between the two groups ( P>0.05), also no difference in APACHE Ⅱ, SIRS and Marshall scores ( P>0.05). The gastric pH was remarkably higher in C+E group when compared to C group (5.02±1.61 vs.2.83±1.08, P<0.001). There was no significant difference in the incidence of peptic ulcer and the rate of positive fecal occult blood between the two groups. ConclusionPPIs therapy did not show benefit on alleviating systemic inflammatory response and clinical scores in SAP patients, and didn’t improve the prevention of peptic ulcer and gastrointestinal hemorrhage.