A 47-year-old man hospitalized for disk surgery received a preoperative injection of hydroxyzine hydrochloride in the upper outer quadrant of the gluteal region. The immediate pain decreased after 3 days but later became incapacitating. Substantial tissue necrosis in the region of the injection was confirmed 4 weeks after the injection, and 100 g of necrotic tissue was excised, leaving the patient with lost muscle mass and a definite limp 2 years later. During the injection of hydroxyzine, the needle penetrated through the gluteal muscle and entered the gluteal artery, causing thrombosis of the artery and necrosis of the gluteus maximus muscle. This case and other reported cases indicate that the use of intramuscular hydroxyzine is contraindicated.