Carbohydrate antigen 19-9 (CA199) has been identified as a tumor marker for pancreatic cancer but also increases in benign lesions of the digestive system. However, literature associated with the relationship between CA199 and acute pancreatitis (AP) is limited. This study aimed to focus on serum CA199 level measurements in AP patients and the associated clinical significance.From January 2006 to December 2015, 1,609 consecutive patients with AP were admitted to our department and included in the study. The relationships among the etiology of AP, the disease severity, the incidence of pancreatic cancer during hospitalization and CA199 levels were analyzed.Serum CA199 levels were measured for 693 of 1,609 AP patients. Of those patients, 186 (26.8%) had elevated CA199 levels (> 37 U/ml). Patients with high CA199 levels were older and had predominantly biliary causes in comparison with patients with normal CA199 levels. There were no definite specific correlations between CA199 levels and disease severity in AP. In addition, serum levels of CA199 positively correlated with serum alanine aminotransferase, aspartate transaminase, glutamyl transpeptidase, alkaline phosphatase and creatinine levels. After stratification, the incidence of pancreatic cancer increased proportionally to CA199 levels in AP patients.Serum CA199 levels was elevated in patients with AP, especially in patients with biliary pancreatitis. AP patients with significantly increased CA199 levels may have a higher risk for the presence of pancreatic cancer. We recommended routinely monitoring CA199 levels during hospitalization for AP patients.