Background Acute pancreatitis is a common and potentially lethal gastrointestinal disease, but literatures for the disease burden are scarce for many countries. Understanding the current burden of acute pancreatitis and the different trends across various countries is essential for formulating effective preventive intervenes. We aimed to report the incidence, mortality, and disability-adjusted life-years (DALYs) caused by acute pancreatitis in 204 countries and territories between 1990 and 2019. Methods Estimates from the Global Burden of Disease Study 2019 (GBD 2019) were used to analyze the epidemiology of acute pancreatitis at the global, regional, and national levels. We also reported the correlation between development status and acute pancreatitis' age-standardized DALY rates, and calculated DALYs attributable to alcohol etiology that had evidence of causation with acute pancreatitis. All of the estimates were shown as counts and age-standardized rates per 100,000 person-years. Results There were 2,814,972.3 (95% UI 2,414,361.3-3,293,591.8) incident cases of acute pancreatitis occurred in 2019 globally; 1,273,955.2 (1,098,304.6-1,478,594.1) in women and 1,541,017.1 (1,307,264.4-1,814,454.3) in men. The global age-standardized incidence rate declined from 37.9/100,000 to 34.8/100,000 during 1990-2019, an annual decrease of 8.4% (5.9-10.4%). In 2019, there were 115,053.2 (104,304.4-128,173.4) deaths and 3,641,105.7 (3,282,952.5-4,026,948.1) DALYs due to acute pancreatitis. The global age-standardized mortality rate decreased by 17.2% (6.6-27.1%) annually from 1.7/100,000 in 1990 to 1.4/100,000 in 2019; over the same period, the age-standardized DALY rate declined by 17.6% (7.8-27.0%) annually. There were substantial differences in the incidence, mortality and DALYs across regions. Alcohol etiology attributed to a sizable fraction of acute pancreatitis-related deaths, especially in the high and high-middle SDI regions. Conclusion Substantial variation existed in the burden of acute pancreatitis worldwide, and the overall burden remains high with aging population. Geographically targeted considerations are needed to tailor future intervenes to relieve the burden of acute pancreatitis in specific countries, especially for Eastern Europe.