Study objective: To evaluate the safety of high-dose IV narcotics in patients requiring analgesia for painful emergency department procedures. Design: Prospective multicenter clinical trial. Setting: Five adult urban EDs. Methods and measurements: All patients received IV meperidine (1.5 to 3.0 mg/kg) titrated to analgesia followed by a painful procedure. Vital signs and alertness scale were recorded at regular intervals, and patients were observed for four hours. Adverse events were monitored and documented. Comparisons between baseline and postanalgesia intervals were made with a repeated measures ANOVA (Dunnett's test). Results: Although statistically significant changes in vital signs and alertness scale occurred, they were not clinically significant. Opiate reversal with naloxone was not needed in any patient, and no significant respiratory or circulatory compromise occurred. Conclusion: This study of 72 patients demonstrates that high-dose narcotic analgesia is appropriate, well tolerated, and safe when used in selected patients before painful procedures in the ED. Narcotic antagonists and resuscitation equipment nonetheless should be available to maximize safety.