Background:Oryz-Aspergillus Enzyme and Pancreatin Tablet is a double-deck digestive enzyme pellet containing Oryz-Aspergillus enzyme and pancreatin that has been widely used for treatment of functional dyspepsia (FD)in clinical practice. However,there is no randomized controlled trial focusing on the efficacy of this agent versus other drugs used for treatment of FD such as prokinetics and proton pump inhibitors (PPI). Aims:To compare the efficacy and safety among Oryz-Aspergillus Enzyme and Pancreatin Tablet,Domperidone Tablet and Esomeprazole Magnesium Enteric-coated Tablet, three drugs with different mechanisms of action on FD,in Chinese population. Methods:A total of 82 Helicobacter pylori-negative outpatients fulfilling the diagnostic criteria of FD in Rome Ⅲ were recruited from Nov. 2015 to Jun. 2016 at the First Affiliated Hospital of Zhejiang Chinese Medical University. These patients were randomly allocated into 3 groups,and received Oryz-Aspergillus Enzyme and Pancreatin Tablet (group A),Domperidone Tablet (group B)and Esomeprazole Magnesium Enteric-coated Tablet (group C)orally for 4 weeks,respectively. The improvement of dyspeptic symptoms and adverse events were observed and recorded. Results:After 4 weeks treatment,the overall efficacies for global symptoms in group A,group B and group C were 93. 1%,88. 9% and 69. 2%,respectively,statistically significant difference was existed among the three groups (P < 0. 05). Domperidone Tablet was effective for postprandial fullness and early satiety;Esomeprazole Magnesium Enteric-coated Tablet was sensitive for epigastric pain,epigastric burning,and belching and regurgitation;the efficacies of Oryz-Aspergillus Enzyme and Pancreatin Tablet for all five dyspeptic symptoms were in between. No adverse events were observed during treatment course. Conclusions:Digestive enzymes,prokinetics and PPI have different sensitive symptoms and optimal indications for treatment of FD. The overall efficacy of Oryz-Aspergillus Enzyme and Pancreatin Tablet is superior to that of prokinetics and PPI.