Altered consciousness may be the first clinical sign of a serious medical problem that requires immediate and intensive therapy to maintain life. There are many causes of the loss of consciousness in the dental office setting, such as, vasodepressor syncope, drug administration or ingestion, orthostatic hypotension, epilepsy, hypoglycemic reaction, acute adrenal insufficiency, cerebrovascular accident, hyperglycemic reaction, acute myocardial infarction, acute allergic reaction and hyperventilation. This is a case report of syncope and coma during endodontic treatment of a maxillary third molar under local infiltration anesthesia in multiple medically compromised patient. The main cause was thought to be hypoglycemic reaction. The patient was transferred to the medical emergency room and cared properly by the emergency medical physicians. The prognosis was good.