Hemorrhage is the most preventable cause of death in civilian and military trauma, and despite tremendous advances in patient transport in the field, survival within the first hour has changed little over the past 40 years. The pathogenesis of trauma-induced coagulopathy is multifactorial, but most authorities believe there is an early depletion of clotting factors. While fresh frozen plasma delivered early in the emergency department has been shown to be beneficial, the rapid onset of trauma-induced coagulopathy suggests advancing this concept to the scene may improve patient outcome. The purpose of this report was to describe the rationale and design of a randomized trial to test the hypothesis that prehospital “plasma-first” resuscitation will benefit the critically injured patient. The rationale includes the possibility that plasma-first resuscitation may be advantageous beyond direct effects on clotting capacity. The study design is based on a ground ambulance system that allows rapid prehospital thawing of frozen plasma.