Toxicity from sedatives (e.g. benzodiazepines) affects cognition, behavior, and functional status. Although a direct antidote is available, it is rarely used due to fears of withdrawal and seizures. At one toxicology center, flumazenil is routinely employed in the emergency department and acute hospital setting. A dose of 0.5 mg is given IV over 30 s, with repeat doses q1-2h as needed to sedated patients with relaxed autonomic indices and peripheral neurologic status. The following reports a six-year retrospective review of the practice and a one-year close observational study of bedside use of the antidote. Flumazenil was given to 731 patients. The overall positive response rate was over 80%. There were no instances of arrhythmias or seizures. In the prospective year, there were 12 instances of side effects out of 212 patients treated. Three patients experienced drooling, 7 experienced transient anxiety, and there were 2 separate episodes of odd behavior upon awakening from coma in a patient with personality disorder. Comorbid anxiety disorders were associated with anxiety upon arousal, but no patient required medical intervention. No clinically significant adverse events occurred with flumazenil administration in patients who chronically used benzodiazepines or had a history of seizures. We conclude that flumazenil is a safe diagnostic and therapeutic antidote for cases of suspected sedativehypnotic toxicity.