Rationale:Midazolam is known as a safe drug and is widely used as a sedative and an anesthetic adjuvant. Therefore, there is a lack of awareness that midazolam can cause anaphylaxis. Midazolam anaphylaxis is rare, and only a few cases have been reported, but such a risk is always present. In this study, we report a case of midazolam anaphylaxis by an intravenous injection, in the prone position, during general anesthesia.Patient concerns:A 62-year-old woman was intravenously administered 1 mg midazolam during general anesthesia, and sudden severe hypotension, bronchospasm, decreased oxygen saturation, erythema, and diarrhea occurred.Diagnosis:Midazolam anaphylaxis was presumptively diagnosed by clinical symptoms and was confirmed by an intradermal test after 9 weeks.Interventions:The patient was treated with 100% oxygen, large volume of fluid, epinephrine, phenylephrine, ephedrine, dexamethasone and prednisolone, ranitidine, and flumazenil.Outcomes:Severe hypotension and decreased oxygen saturation were resolved within 20 minutes of the onset of anaphylaxis, and the patient was discharged after 3 days without any sequelae.Lessons:Midazolam anaphylaxis is very rare, but it can happen always. Therefore, the possibility of anaphylaxis due to midazolam should be considered and always be prepared for treatment.