Background There are no published reports in Canada examining paramedic use of ketamine for highly agitated patients or excited delirium syndrome. We employed a Plan, Do, Study, Act (PDSA) quality improvement approach to evaluate the safety and effectiveness of advanced care paramedic administered intramuscular (IM) ketamine for patients with extreme agitation in the out-of-hospital setting. Methods Data were prospectively collected from July 2018 to January 2019 when advanced care paramedics with specific training administered IM ketamine as an alternative to midazolam. Paramedics used a clinical audit form to document the ketamine dose, patient response on the Richmond Agitation Sedation Scale (RASS) at time intervals, adverse effects, and any airway management interventions they performed. Results Thirty-three patients received either 4 mg/kg or 5 mg/kg of ketamine. Combining data for both doses, the median change in RASS score at 5 minutes post-ketamine was 3 (range 0 to 8) and statistically significant for each dose. There were seven cases (21%) with reported adverse effects including SpO2 <90% (3/7), hypersalivation (3/7), trismus or teeth grinding (2/7), muscular rigidity (1/7) and laryngospasm (1/7). Statistical analysis confirmed that the incidence of adverse events was not dose dependent. Basic airway management was performed in one-third of all cases. Conclusion We piloted the implementation of ketamine for sedation in our paramedic system by employing a PDSA cycle. Ketamine 5 mg/kg IM provided effective control of acutely agitated patients with adequate sedation at 5 minutes post-delivery. Any adverse events that occurred as a result of IM ketamine were readily managed with basic airway management interventions.