Misoprostol is widely used in daily practice for induction of labor and cervical dilatation prior to intrauterine procedures, including dilatation and curettage or hysteroscopy. Anaphylactic shock to intravaginal misoprostol can occur not only in pregnant women, as reported in 2 previous cases, but also in a non-pregnant, perimenopausal woman, as in the case described herein. A 49-year-old woman received vaginal misoprostol for cervical ripening prior to hysteroscopic myomectomy and experienced anaphylactic shock. Two 400 μg doses of misoprostol 6 hours apart caused uncontrolled shaking and high fever followed by shock. In conclusion, the possibility of anaphylactic shock should be considered in patients with sudden hypotension following misoprostol administration. Prompt identification and management are crucial to prevent morbidity and mortality following an anaphylactic shock to misoprostol.