Acute pancreatitis is a serious gastrointestinal disease that is an important target for drug safety surveillance. Little is known about the accuracy of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) codes for acute pancreatitis in the United States, or their performance in specific clinical settings. We conducted a validation study to assess the accuracy of acute pancreatitis ICD-10 diagnosis codes in inpatient, emergency department, and outpatient settings. We reviewed electronic medical records for encounters with acute pancreatitis diagnosis codes in an integrated healthcare system from October 2015 to December 2019. Trained abstractors and physician adjudicators determined whether events met criteria for acute pancreatitis.