Patients presenting to the emergency department with acute agitation frequently require physical and chemical restraint. To determine the efficacy of lorazepam vs. droperidol, we conducted a prospective, randomized study of violently agitated patients requiring chemical restraint. Patients were randomized to receive either lorazepam or droperidol i.v. A six-point sedation scale was used. Sedation scores were recorded at time 0, 5, 10, 15, 30, and 60 min. Vital signs were compared at time 0 and at 60 min. Repeat dosages of each drug could be given at 30 min. Toxicology screen, ethanol and creatinine phosphokinase levels were obtained. A total of 202 patients were evaluated. One hundred patients received lorazepam and 102 patients received droperidol. Agitation was attributed to methamphetamine toxicity in 146 patients (72%), cocaine toxicity in 28 (14%), psychiatric illness in 20 (10%), and ethanol withdrawal in 8 (4%). Ethanol intoxication was present in 98 patients (49%). Both drugs had similar sedation profiles at 5 min. Patients receiving droperidol had significantly lower sedation scores at times 10, 15, 30, and 60 than lorazepam. More repeat doses of lorazepam were given (40) than droperidol (8) at 30 min. We conclude that droperidol produces a more rapid and better sedation than lorazepam at the doses used in this study in agitated patients requiring chemical restraint. Lorazepam is more likely to require repeat dosing than droperidol. Methamphetamine toxicity was present in the majority of patients in this study.