The coronavirus disease 2019 (COVID-19) pandemic has led to overcrowding in many emergency departments (EDs). The present single-center, prospective, interventional study (conducted at Bichat University Medical Center (Paris, France)) was designed to assess the impact of self-administered, inhaled, low-dose methoxyflurane on trauma pain in a pre-ED fast-track zone dedicated to the management of lower-acuity non-COVID-19 patients. In the first phase of the study, the control group consisted of patients with mild-to-moderate trauma pain, for whom the triage nurse initiated pain management (based on the World Health Organization (WHO)’s analgesic ladder). In the second phase, the intervention group consisted of similar patients who self-administered methoxyflurane as an adjuvant to the standard analgesic ladder. The primary endpoint was the numerical pain rating scale (NPRS) score (from 0 to 10) recorded at different time points during the patient’s care (T0: arrival in the ED, T1: exit from the triage box, T2: in the radiology department, T3: clinical examination, and T4: discharge from the ED). The level of agreement between the NPRS and the WHO analgesic ladder was assessed by the calculation of Cohen’s kappa. Pairwise comparisons of continuous variables were performed with Student’st-test or a non-parametric Mann–Whitney U test. Changes over time in the NPRS were analyzed in an analysis of variance (with Scheffe’s post hoc test if a pairwise comparison was significant) or a non-parametric Kruskal–Wallis H test. In all, 268 and 252 patients were included in the control and intervention groups, respectively. The two groups had similar characteristics. The level of agreement between the NPRS score and the analgesic ladder was high in both the control and intervention groups (Cohen’s kappa: 0.74 and 0.70, respectively). The NPRS score decreased significantly between T0 and T4 in both groups (p< 0.001), but the decrease between T2 and T4 was significantly greater in the intervention group (p< 0.001). The proportion of patients still in pain on discharge was significantly lower in the intervention group than in the control group (p= 0.001). In conclusion, a combination of self-administered methoxyflurane and the WHO analgesic ladder improves pain management in the ED.