Introduction: Pain is a significant driver of demand in emergency care and 65% of adult patients with trauma also report moderate to severe pain. Inhaled low dose methoxyflurane (MEOF) a rapid-acting patient administered inhalational analgesic was recently approved in Canada for the short-term relief of moderate to severe acute pain associated with trauma or interventional medical procedures in conscious adult patients. This study will generate real-world evidence to complement the global clinical development program through evaluation of the effectiveness of MEOF in Canadian emergency departments. Methods: This is a phase IV, prospective open label, multi-centre study. Approximately 100 adult (≥18 yrs) patients with moderate to severe acute pain (NRS0-10≥4) associated with single system trauma will be enrolled at 5-10 EDs across Canada. Patients will receive a single treatment of up to 2 x 3 mL MEOF (2nd 3 mL to be provided only upon request), self-administered by the patient under medical supervision. Rescue medication will be permitted at any time, if required. Results: Planned Assessments and Outcome Measures: Pain will be assessed using the NRS0-10 at 4 time points: screening/triage, 5 minutes and 20 minutes post-start of administration (STA) of MEOF, and when ready for discharge. Secondary assessments will include the speed of action of analgesia (from STA of MEOF); patient and physician satisfaction with treatment (as assessed through Global Medical Performance (GMP) at 20 minutes post-STA and when ready for discharge); patient and physician fulfilment of pain relief expectations (assessed when ready for discharge); use of rescue medication and treatment-emergent adverse events. Exploratory outcomes will include the time to disposition, time to readiness for discharge and responder analysis. The primary outcome measure will be the change in pain intensity over 20 minutes from the start of administration of MEOF as measured on the NRS0-10. Conclusion: We report on the methodology of a phase IV, prospective open label, multi-centre study, evaluating the use of MEOF for the management of acute traumatic pain in Canadian Emergency Departments.