In recent years, the treatment of acute pancreatitis has significantly improved. However, there is still room for improvement, especially on rarer and less known complications, which is the focus of this dissertation. Approximately 20% of patients develop necrotizing pancreatitis, where the pancreas or the surrounding fat tissue dies. First, it is demonstrated that antibiotics are excessively and incorrectly used in these patients, and we found that the pancreatic duct was disrupted in at least one in four patients with necrotizing pancreatitis, especially in patients with central or near-total pancreatic necrosis and a high inflammatory protein level <48 hours after admission. This disruption was associated with worse short- and long-term outcomes. In one out of six patients with necrotizing pancreatitis, perforation or fistula formation to the gastrointestinal tract occurred, the duodenum and colon are most affected. Risk factors were a high inflammatory protein level <48 hours and organ failure <1 week after admission. Perforation or fistula formation to the stomach or duodenum was more often conservatively treated and was associated with fewer intensive care admissions and less persistent organ failure. When the small and/or large intestine was involved, new organ failure occurred more often, and surgical intervention was more frequently required. Identifying the cause is important to prevent future recurrences. In patients without an apparent cause, a cause was found in one-third of cases through endoscopic ultrasound. Furthermore, we showed that the risk of gallstone-related problems was lower if gallbladder removal occurred within 10 weeks after discharge, and the risk of gallstone-related pancreatitis was lower with gallbladder removal within 8 weeks after discharge. The insights from this dissertation have led to new studies aimed at improving the treatment and quality of life of patients with acute pancreatitis and helping to control rising healthcare costs.