Background: Traumatic musculoskeletal injury (TMsI) often leads to chronic pain and post-traumatic stress disorder (PTSD). This study examined factors of a modified diathesis-stress model in the development of PTSD symptoms following TMsI. Methods: 205 patients were recruited in this prospective, observational study. Within 14 days of injury, participants completed an in-hospital questionnaire investigating acute symptoms of anxiety, depression, pain, and PTSD. Results: Logistic regression identified multiple factors associated with symptoms of PSTD (p<.0001). Neuropathic pain (odds ratio[OR]=1.091, 95% confidence interval[CI] 1.020-1.168), general anxiety (OR=1.176, 95%CI 1.046-1.318), pain anxiety (OR=1.056, 95%CI 1.018-1.094), and pain catastrophizing (OR=1.168, 95%CI 1.016-1.348) were associated with acute symptoms of PTSD. Conclusions: The results support the modified diathesis-stress model indicating that neuropathic pain, general anxiety, pain anxiety, and pain catastrophizing are associated with symptoms of PTSD. Future studies should examine the influence of these acute factors on the development of chronic pain and PTSD following TMsI.