Anaphylaxis is a rapid and severe reaction to a trigger that is characterized by skin, mucosal, and cardiorespiratory changes. A minority of patients exhibit a biphasic anaphylactic reaction (BAR). Tirzepatide is a dual incretin receptor analog approved for the treatment of type 2 diabetes mellitus (T2DM). Allergic reactions to tirzepatide were reported during clinical trials, but none were severe enough to be characterized as an anaphylactic reaction. We describe a case of a BAR to tirzepatide.