Eperisone is a widely used muscle relaxant and believed to be relatively free of adverse drug reactions. However, a rare case of fatal anaphylaxis has been reported in the literature. Poor awareness due to its rarity and combined administration with other drugs are the major hurdles in diagnosing eperisone-induced anaphylaxis. We experienced 3 cases of immediate hypersensitivity reaction oc-curring after eperisone administration. Case 1, a 63-year-old female, was admitted via the Emergency Department with urticaria, generalized erythroderma, sore throat, chest discomfort, and dyspnea within 1 hour after administration of common cold remedy. Case 2, a 58-year-old male, visited our allergy clinic to detect culprit drugs. He experienced itching, urticaria, hypotension for several hours after administration of the pills for back pain in the last 3 years. Case 3, a 58-year-old male developed urticaria and dyspnea after administration of medication for a headache. He also experienced urticaria and facial edema after administration of the common cold remedy. Among the medications, eperisone hydrochloride was proven as the culprit drug and others were excluded through oral provocation tests. We advised them to avoid eperisone and issued drug safety card. Clinicians should be aware that eperisone hydrochloride is a potential culprit agent of fatal anaphylaxis.