OBJECTIVES: To analyze the current utilization and expenditure of reimbursed digestive enzyme agents (DEs) in Taiwan. METHODS: The encrypted claim database of National Health Insurance (NHI) was used to analyze the prescription patterns and the expenditure of DEs for types of diseases, healthcare specialties, levels of medical institution, and insured BNHI branch. RESULTS: We identified that 29 DEs, within 15 groupings, are reimbursed by NHI up to 2011. Given that most DEs were developed in earlier stage, while only 2 items were approved by the Taiwan Food and Drug Administration after 2000, these approved items had broader scope of approved indications and limited evidence on their clinical efficacy. According to the analysis of 2001-2010 NHI databases, the most enzymes prescribed disease was gastroenteritis, related uncomfortable symptoms, and so forth. Over the ten years, the number of medical orders increased from 22.77 million to 46.71 million. Medical costs increased from more than NT$ 1 hundred million to over NT$ 2 hundred million. The highest usage rate of medical orders, by specialties, is 64% in Internal Medicine, especially in Gastroenterology and in General Medicine. The second is 7% to 9.6 % in Family Medicine. The usage rate is increasing each year in Surgery, from 4.13% in 2011 to 9.27% in 2010. The usage rates of medical order by 15 groupings have various trends of levels between different medical institution, and different insured BNHI branch. CONCLUSIONS: Some countries’ pharmaceutical benefits programs such as Australia, Canada, or U.S. listed DEs for pancreatic insufficiency due to chronic pancreatitis, carcinoma of the pancreas, or cystic fibrosis, however, those reimbursed by Taiwan NHI had broader scope of indications. In addition to more medical orders prescribed by varied health care specialties, we observed the expenditure increased by approximately two times over the past 10 years.