Background <p>Anaphylaxis caused by intravenous acetaminophen is extremely rare, but a few case reports have identified mannitol, an excipient, as the causative component. Since mannitol is widely present in medications and foods, distinguishing the true antigen is essential to prevent recurrence.</p> Case Presentation <p>A 67-year-old woman developed anaphylaxis with pulseless electrical activity during ophthalmic surgery after intravenous administration of acetaminophen (Acelio®). Allergy testing revealed positive reactions to both Acelio® and acetaminophen in skin tests and the basophil activation test, while reactions with mannitol were negative. Acetaminophen was confirmed as the causative agent. Hence, the patient was instructed to avoid only acetaminophen.</p> Conclusions <p>Accurate identification of the causative component in intravenous acetaminophen formulations is critical. Clarifying whether the reaction is due to the active ingredient or an excipient such as mannitol helps prevent unnecessary drug restrictions and expands future treatment options.</p>