Proton pump inhibitors (PPIs) decrease pancreatic exocrine secretions. There has been interest in the impact of their short-term in-hospital administration on acute pancreatitis (AP) outcomes. It is unknown whether long-term use affects AP outcomes. We investigated the association between chronic PPI use and short-term AP outcomes. We included all (2308) patients admitted with a primary diagnosis of AP (625 on chronic PPI use) between January 2008 and June 2021 and evaluated any association between chronic PPI use and 30-day all-cause mortality by univariate logistic regression. Compared to non-users, patients on chronic PPIs were older (p < 0.001) and had a higher Charlson Comorbidity Index score (p < 0.001). Mortality rates at 30 days were 1.6% in chronic PPI users and 4.4% in non-users (OR 0.35; 95% CI, 0.17-0.66; p < 0.002). [Correction added on 18 February 2025, after first online publication: Mortality rates at 30 days in chronic PPI users and non-users were updated in this version.].