Introduction: Insufficient analgesia affects around 50% of emergency department patients. The use of a protocol helps to reduce the risk of oligoanalgesia in this context. Our objective was to describe the feasibility and efficacy of a multimodal analgesia protocol (combining paracetamol, oxycodone, and inhaled low-dose methoxyflurane) initiated by triage nurse. Methods: We performed a prospective, observational study in the emergency department at Grenoble Alpes University Hospital (Grenoble, France) between October 2017 and April 2018. Non severe adult trauma patients with a numerical pain rating scale (NRS) score ≥4 and receiving MEOF were included. The primary efficacy criterion was the proportion of patients with an NRS score ≤3 at 15min post-administration. Pain intensity was measured for 60 min as well as during radiography. Data on adverse events and satisfaction were also recorded. Data are presented as median [interquartile (IQR)] and were compared using non parametric tests. Results: A total of 200 adult patients were included (age: 32 [IQR: 23–49] years; 126 men (63%)). Patients presented at triage with a pain score of 7 [IQR: 6-8]. Sixty-six patients (33%) reported an NRS score ≤3 at 15 min post-administration. The time required to achieve a decrease of at least 2 points in the NRS score was 10 [IQR 5–20] min. The pain intensity was 4 [IQR: 2–5] before radiography and 4 [IQR: 2–6] during radiography. Adverse events were frequent (n = 128, 64%), mainly dizziness. No serious adverse events were reported and 89% of minor adverse events resolved at one hour. Both patients and health care providers reported good levels of satisfaction. Conclusion: The administration of a nurse-driven multimodal analgesia protocol combining paracetamol, oxycodone, and low-dose methoxyflurane was feasible on triage. It rapidly produced long-lasting analgesia in adult trauma patients.