Recent evidence demonstrated that prehospital plasma in patients at risk of hemorrhagic shock was safe for ground transport and resulted in a 28-day survival benefit for air medical transport patients. Whether any beneficial effect of prehospital plasma varies across injury mechanism remains unknown.We performed a secondary analysis using a harmonized dataset derived from two recent prehospital plasma randomized trials. Identical inclusion/exclusion criteria and primary/secondary outcomes were employed for the trials. Prehospital time, arrival shock parameters and 24-hour transfusion requirements were compared across plasma and control groups stratified by mechanism of injury. Stratified survival analysis and Cox hazard regression were performed to determine the independent survival benefits of plasma across blunt and penetrating injury.Blunt patients had higher injury severity, were older and had a lower GCS. Arrival indices of shock and coagulation parameters were similar across blunt and penetrating injury. The percentage of patients with a prehospital time less than 20 mins was significantly higher for penetrating patients relative to blunt injured patients (28.0% vs 11.6%, p<0.01). Stratified Kaplan-Meier curves demonstrated a significant separation for blunt injured patients (n=465, p=0.01) with no separation demonstrated for penetrating injured patients (n=161, p=0.60) Stratified Cox hazard regression verified, after controlling for all important confounders, that prehospital plasma was associated with a 32% lower independent hazard for 28 day mortality in blunt injured patients (HR 0.68, 95% CI 0.47-0.96, p= 0.03) with no independent survival benefit found in penetrating patients (HR 1.16, 95%CI 0.4-3.1, p=0.78).A survival benefit associated with prehospital plasma at 24 hours and 28 days exists primarily in blunt injured patients with no benefit shown in penetrating trauma patients. No detrimental effects attributable to plasma are demonstrated in penetrating injury. These results have important relevance to military and civilian trauma systems.Original ArticleSecondary Analysis LEVEL OF EVIDENCE: I.