Eluxadoline has emerged as an effective treatment option for patients with diarrhea- predominant irritable bowel syndrome (IBS-D). It was approved by the Food and Drug Administration (FDA) in May 2015 for treatment of IBS-D. It is a p-opioid receptor agonist and 6-receptor antagonist that acts locally in the gastrointestinal (GI) tract. In recently published phase IlIl IBS-3001 and IBS- 3002 trials, eight patients experienced abdominal pain due to sphincter of Oddi dysfunction (SOD), and one patient had acute pancreatitis, thought to be related to eluxadoline. Here, we describe a patient with eluxadoline- induced pancreatitis, the first case we know of to be reported outside of phase Ill clinical trials. Interestingly, only patients with prior cholecystectomy developed SOD and acute pancreatitis in the IBS 3001/3002 trials which also stands true with our patient. The enthusiasm with the efficacy of this drug should not have clinicians disregard the potential adverse effects, particularly serious ones, such as acute pancreatitis. We expect more cases of eluxadoline-induced pancreatitis and SOD to be reported, and future studies should focus on better understanding this association so as to guide treatment recommendations.