Background: Most medical helicopter rescue interventions concern trauma patients requiring rapid onset and powerful analgesia. Conventional intravenous (IV) analgesia meets this objective but inserting an IV catheter on the field can be hazardous. Oral transmucosal fentanyl (OTFC) could be an interesting alternative. Our objective was to evaluate the feasibility, safety, and efficacy of this treatment. Method: We conducted a monocentric prospective study from February 1st 2009 to August 31st 2010. For all trauma patients with a verbal rating scale (VRS) ≥3/10, the physician administered either transmucosal fentanyl (200 μg for patients weighing less than 40kg or 400 μg for patients above 40 kg) or IV analgesia of its choice. Adverse events and VRS were monitored every 10 minutes. Results: A total of 226 patients were included. Oral transmucosal fentanyl was administered to 31 patients not showing any adverse effect. At 20 minutes after administration, the VRS median decreased from 8 to 4 in the transmucosal group and for 7 to 3 in the IV group where morphine was the medication mostly used. In the transmucosal group, an additional IV medication "rescue analgesia" was required in 24 % of patients. This rate was 39 % in patients where the VRS was initially above 8. There was no statistically significant difference concerning intervention time in both groups. Conclusion :Transmucosal route can be used during helicopter rescue interventions in the initial management of trauma pain. At the doses used in this study, adverse effects were rare and the efficacy of transmucosal analgesia was not different from the IV route. Oral transmucosal fentanyl could be a considerable safe alternative to IV analgesia in hostile environments.