Introduction: Paramedics are required to manage combative patients. In order to do so safely, chemical sedation may be required. Advanced Care Paramedics in our EMS system utilize midazolam for chemical restraint. Our previous research has shown that midazolam appears to have few prehospital adverse events (AEs) associated with its use. However, it required multiple dosages in 33.3% of patients and was deemed ineffective in 15.1% of patients that received it in the prehospital setting. Objective: To determine Emergency Department (ED) AEs associated with the prehospital use of midazolam in combative patients and determine the efficacy of this agent as a chemical restraint during the first hour of the ED stay. Methods: A retrospective chart review of paramedic calls from 2 urban centers, from January 2012 to December 2015 was completed. All cases of combative patients were examined. Patients were excluded if they were 17 or younger. Ambulance call records were linked to the patient’s ED chart. ED charts were reviewed and a priori endpoints were extracted. Results: Of approximately 350,000 calls, there were 269 patients that were combative. Of these, 186 (69.1%) received midazolam in the prehospital setting. During the first hour of their ED stay, 68 (36.5%) required further sedation, while 118 (63.4%) patients did not. Of the 186 patients who received midazolam in the prehospital setting there was one death and one AE in the ED (defined as hypotension, bradypnea, or need for airway intervention). After further review of the charts, both AEs were deemed likely resulting from underlying pathology and not related to the use of midazolam. The average ED Length of stay (LOS) was 7.6 hours for all patients. A total of 82 (44.1%) were admitted to hospital with a mean in hospital LOS of 13.1 days. Conclusion: Prehospital use of midazolam for combative patients appears to be safe, with no reported delayed AEs. 36.5% of this cohort required further sedation within 1 hour of their ED arrival. This supports previous findings that midazolam was ineffective in 15.1 % of prehospital combative patients. Further study is required to determine midazolam’s efficacy and AE profile compared to other prehospital agents in order to ensure optimal safety of both patients and paramedics.