The vast majority of individuals who come to the emergency department (ED) for care after a motor vehicle collision (MVC) are diagnosed with musculoskeletal strain only and are discharged to home. A significant subset of this population will still develop persistent pain and posttraumatic psychological sequelae may play an important role in pain persistence. We conducted a multisite longitudinal cohort study of adverse post-traumatic neuropsychiatric sequelae among patients seeking ED treatment in the aftermath of a traumatic life experience. We report on a sub-group of patients (n=666) presenting after an MVC, the most common type of trauma and we examine associations of socio-demographic and MVC characteristics, and persistent pain 8weeks after MVC. We also examine the degree to which these associations are related to peritraumatic psychological symptoms and 2-week acute stress reactions using an applied approach. Eight-week prevalence of persistent moderate or severe pain was high (67.4%) and positively associated with patient sex (female), older age, low socioeconomic status (education and income) and pain severity in the ED. Peritraumatic stress symptoms (distress and dissociation) appear to exert some influence on both acute pain and the transition from acute to persistent pain. The early aftermath of an MVC may be an important time period for intervening to prevent and reduce persistent pain. Substantial variation in mediating pathways across predictors also suggests potential diverse and complex underlying biological and psychological pathogenic processes are at work in the early weeks following trauma. The first several days after trauma may dictate recovery trajectories. Persistent pain, pain lasting beyond the expected time of recovery, is associated with pain early in the recovery period, but also mediated through other pathways. Future work is needed to understand the complex neurobiological processes in involved in the development of persistent and acute post-traumatic pain.