Objective: To determine whether prehospital nonsteroidal anti-inflammatory drug (NSAID) use may lead to a reduced incidence of trauma-induced coagulopathy (TIC) in severely injured patients. Background: TIC is present in up to a quarter of severely injured trauma patients and is linked to worse outcomes after injury. Evidence linking TIC to inflammation has emerged; however, the mechanism behind this association is still under investigation. NSAIDs are commonly used anti-inflammatory drugs, but their effects on TIC and outcomes after injury are largely unexplored. Methods: We performed a secondary analysis of the Inflammation and the Host Response to Injury Large Scale Collaborative Program (Glue Grant) data set. Prehospital medications and comorbidities were analyzed by logistic regression analysis for association with TIC as defined by laboratory (international normalized ratio >1.5) or clinical (transfusion >2 units of fresh frozen plasma or >1 pack of platelets in 6 hours) parameters. Results: Prehospital NSIAD use was independently associated with a 72% lower risk of TIC and was the only medication among 15 analyzed to retain significance in the model. Stepwise logistic regression also demonstrated that preadmission use of NSAIDs was independently associated with a 66% lower risk of clinically significant coagulopathy. These findings were independent of comorbid conditions linked to NSAID use. Conclusions: NSAID use before admission for severe injury is associated with a reduced incidence of TIC. These findings provide further evidence to a potential leak between TIC and inflammation.