Background: The aim of this study was to examine the role of pre-trauma, traumatic event, and peri-traumatic psychological characteristics on post-motor vehicle accident (MVA) Posttraumatic Stress Disorder (PTSD) and depression. Methods: The sample comprised 333 (54% female) hospital accident and emergency attendees who completed a self-report postal screening survey approximately 1-month post-accident and 128 (62% female) participants who completed a follow-up survey at 3-months. Results: Path analysis (Model 1) showed that dissociation partially mediated the relationship between past emotional problems and initial post-MVA distress, as well as between fear of dying and levels of distress. Level of alertness and perceived accident severity had no direct effects on post-MVA distress. However, higher levels of exposure contributed to distress predominantly in the presence of high levels of fear and subsequent dissociative experiences. When ongoing PTSD and depression symptoms were included (Model 2), feeling depressed/sad at 1-month was the strongest predictor of both PTSD and depression symptom severity at 3-months post-MVA, explaining 53% and 40% of the variance, respectively. Dissociation remained an important mediating variable at both time points. Conclusions: These models show the influence of previous emotional vulnerability factors and the important mediating role of peri-traumatic experiences (in the presence of fear due to increased levels of accident severity) on post-MVA morbidity. Additionally, MVA survivors who report feeling depressed/sad 1-month after their accident are at greater risk of developing both PTSD and depression. Depression and Anxiety 28:218–226, 2011. © 2011 Wiley-Liss, Inc.