There is limited literature on non-invasive mechanical ventilation (NIMV) in patients with polytrauma-related acute respiratory failure (ARF). Despite an increasing worldwide application, there is still scarce evidence of significant NIMV benefits in this specific setting, and no clear recommendations are provided. We performed a systematic review, and a search of clinical databases including MEDLINE and EMBASE was conducted from the beginning of 1990 until today. Although the benefits in reducing the intubation rate, morbidity and mortality are unclear, NIMV may be useful and does not appear to be associated with harm when applied in properly selected patients with moderate ARF at an earlier stage of injury by experienced teams and in appropriate settings under strict monitoring. In the presence of these criteria, NIMV is worth attempting, but only if endotracheal intubation is promptly available because non-responders to NIMV are burdened by an increased mortality when intubation is delayed.