Abstract As obesity is increasing in prevalence and its associated morbidity and mortality are escalating worldwide, medications like tirzepatide are frequently used for weight loss benefits in patients without diabetes. Tirzepatide has rarely been associated with acute pancreatitis, but there are no reported cases of fulminant, necrotizing pancreatitis resulting in fatality. We present a case of fatal, fulminant, necrotizing pancreatitis in a 64-year-old low-risk female patient with recent tirzepatide initiation. Prior to starting this medication, a case-by-case risk benefit analysis should be performed for each patient. The importance of this should be emphasized by making necrotizing pancreatitis a boxed warning for tirzepatide.