Central anticholinergic syndrome (CAS) can be caused by many anesthetic drugs. Early diagnosis and treatment are very important because untreated CAS may result in a life-threatening condition. Physostigmine, though not available in Korea, is the only drug which can confirm and treat CAS. A forty five year old patient underwent open heart surgery due to patent foramen ovale. Anesthetic agents which were used for anesthetic induction and maintenance were midazolam, fentanyl and isoflurane. Following anesthesia, he showed irritated and excited behavior and delayed recovery from anesthesia more than 3 h after operation in the ICU, even though flumazenil and naloxone were given to rule out the residual anesthetic effect. After physostigmine 4 mg was administered intravenously, he calmed down and became more coherent. There was no evidence of neurologic deficit in the following brain MRI and neurologic examination. We report the first case of CAS confirmed with physostigmine in Korea.