Treatment of acute pancreatitis remains a challenge, with therapy focused on supportive care and treating the inciting etiology. Tumor necrosis factor-alpha (TNFα) inhibitors have shown promising results treating acute pancreatitis in animal models, but they have not been evaluated in human trials yet. A 25-year-old woman presented with ulcerative colitis. She was unresponsive to immunomodulators and developed acute pancreatitis shortly after initiation of a TNFα inhibitor. Her symptoms subsided after discontinuation of the medication, but reemerged when a different TNFα inhibitor was introduced to control her ulcerative colitis. Other potential etiologies were investigated and clinically excluded by laboratory and imaging studies.