Background and aims Acute trauma pain is one of the most important patient complaints in emergency department (ED). Previous studies lack data on fentanyl sublingual (FSL) in comparison to fentanyl intravenous (FIV) for acute moderate to severe trauma pain in ED and on differences between female and male patients using FSL or FIV.

We hypothesized that FSL is not inferior to FIV and no differences in terms of efficacy and side effects in the management of acute moderate to severe pain exist between female and male patients.

Methods A prospective, randomized, double-blind, single-center, non-inferiority clinical trial was performed including 108 adults (54 females and 54 males) with acute trauma pain ≥4 on numeric rating scale (NRS) at ED triage. They received either fentanyl intravenous (1 µg kg^-1) or sublingual (100 µg) and the correspondent placebo. NRS, SpO₂, respiratory frequency, blood pressure and heart rate were assessed before and 5, 10, 20, 30 and 60 minutes after fentanyl administration and side effects during observation.

Results Analgesia was not different but side effects were more present in the FIV group. There are no differences between female and male patients either in analgesia or presence of side effects, adverse events, need for rescue dose and patient satisfaction.

Conclusions This study compares FSL and FIV for acute moderate to severe trauma pain in women and men in emergency department. The results indicate no sex differences in analgesia and side effects. This investigation could help reduce the lack of knowledge regarding sex differences in opioid use.