This study examined the relationship between prior history of traumatic events, life threat, and injury severity experienced during a motor vehicle accident (MVA), and posttraumatic stress disorder (PTSD) assessed 1 month after the accident. In addition, initial urinary cortisol levels after the accident were examined as a possible mediator of this relationship. Fifteen-hour urinary cortisol samples were collected from MVA victims upon admission to the trauma unit. In the hospital, subjective life threat was measured and objective Injury Severity Scores (ISSs) were computed. One month after the accident, participants were assessed for prior history of traumatic experiences, presence of acute PTSD, and levels of intrusive and avoidant thoughts and behaviors. Victims, who met PTSD diagnostic criteria, reported more prior traumatic events, and significantly greater life threat despite receiving significantly lower ISSs than victims who did not develop PTSD. The relationships between ISSs and PTSD symptoms and prior trauma history and PTSD symptoms were mediated by cortisol levels. Results suggest that cortisol levels in the acute aftermath of a traumatic event may serve as a mechanism through which various factors may increase risk for PTSD.