Introduction: Paramedics are often required to manage violent or combative patients. In order to do so safely, chemical sedation may be required. There are a number of pharmacologic agents which may be used. However, there is a paucity of evidence as to the optimal agent. Objective: To provide a descriptive analysis of a single base hospital’s experience with combative patients and to determine the efficacy and any adverse events (AEs) in the prehospital setting, associated with midazolam use in these patients. Methods: A retrospective chart review of ambulance calls from 2 urban centers, from January 2012 to December 2015 was completed. All cases of combative patients were filtered and manually examined. Patients were excluded if they were 17 or younger. A priori data points were abstracted by trained research personnel from the ambulance call record. Results: Of approximately 350,000 calls over the study period, there were 269 patients that were combative. Of these, 186 (69.1%) received midazolam for sedation. Multiple doses were required in 33.3% of patients. Depending on route of administration, the average total dose administered was 6.27 mg (SD 3.98 mg) intramuscular, 10.7 mg (SD 4.00 mg) intranasal and 4.95 mg (SD 3.81 mg) intravenous. Midazolam was documented as effective in treating the combativeness in 133 (71.6%), ineffective in 28 (15.1%), and not documented in 25 (13.4%) calls. AEs post midazolam administration, defined as hypotension, bradypnea, bradycardia, or need for airway intervention, were encountered in 3 (1.61%) calls (respiratory rate of 8, hypotension of 88/59 that responded to intravenous fluid and asymptomatic bradycardia of 59). There was a trend of increasing number of combative patients each year over the study period, with a significant difference in the number of combative calls requiring midazolam administration between 2012 and 2015 (50.0% vs 72.8%, p=0.007). Conclusion: Prehospital use of midazolam for combative patients appears to be safe, with minimal AEs. However, midazolam was ineffective in 15.1% and a third of all patients required multiple doses, prolonging the combative period and compromising paramedic and patient safety. Further research is warranted for this cohort’s emergency department (ED) sedation needs and any associated AEs within 1 hour of ED arrival.