Background: Among trauma patients relatively high prevalence rates of posttraumatic stress disorder (PTSD) have been found. To identify opportunities for prevention and early treatment, predictors and course of PTSD need to be investigated. Long-term follow-up studies of injury patients may help gain more insight into the course of PTSD and subgroups at risk for PTSD. The aim of our long-term prospective cohort study was to assess the prevalence rate and predictors, including pre-hospital trauma care (assistance of physician staffed Emergency Medical Services (EMS) at the scene of the accident), of probable PTSD in a sample of major trauma patients at one and two years after injury. The second aim was to assess the long-term course of probable PTSD following injury. Methods: A prospective cohort study was conducted of 332 major trauma patients with an Injury Severity Score (ISS) of 16 or higher. We used data from the hospital trauma registry and self-assessment surveys that included the Impact of Event Scale (IES) to measure probable PTSD symptoms. An IES-score of 35 or higher was used as indication for the presence of probable PTSD. Results: One year after injury measurements of 226 major trauma patients were obtained (response rate 68%). Of these patients 23% had an IES-score of 35 or higher, indicating probable PTSD. At two years after trauma the prevalence rate of probable PTSD was 20%. Female gender and co-morbid disease were strong predictors of probable PTSD one year following injury, whereas minor to moderate head injury and injury of the extremities (AIS less than 3) were strong predictors of this disorder at two ye Conclusions: Up to two years after injury probable PTSD is highly prevalent in a population of patients with major trauma. The majority of patients suffered from prolonged effects of PTSD, underlining the importance of prevention, early detection, and treatment of injury-related PTSD.