A prospective observational study in an inner-city teaching hospital was conducted to evaluate the safety and efficacy of intravenous methohexital (MTX) in the emergency department (ED). Pulse oximetry, vital signs and Glasgow Coma Scale (GCS) scores were recorded serially for 30 minutes after the administration of MTX to 76 adult patients. Likert scales of 1 to 5 were used to record the physician's assessment of the adequacy of sedation and the patient's assessments of recall and pain of the procedure. Patients received an average of 88 +/- 21 mg of MTX for a variety of indications (orthopedic procedures, 78%; sedation for other procedures, 14%; intubation, 5%; and psychiatric interview, 3%). No patient had clinically significant changes in heart rate or blood pressure. Eight (10.5%) had apnea, although only one patient had oxygen saturations of less than 90%. Each episode was brief and easily managed with bag-valve-mask ventilation. Risk factors for apnea included a history of alcoholism (P = .0003) and recent recreational narcotic use (P = .0139). Patients were maximally sedated in an average of 37 +/- 42 seconds. In the subset of initially alert patients, GCS scores decreased from 15 at baseline to 5.9 +/- 4.5. The physician's assessment of the adequacy of sedation was excellent (4.7 +/- 0.7). Patients reported little recall (1.3 +/- 0.9) or pain (1.3 +/- 0.8). It was concluded that MTX caused clinically insignificant changes in hemodynamics or oxygenation, although respiratory depression did occur; significant respiratory depression was brief and easily managed. MTX provided rapid and excellent levels of sedation with little or no patient recall or pain.