Research suggests that exposure therapy provided in the hours immediately following trauma exposure may prevent posttraumatic stress disorder (PTSD). This case report presents data on an at-risk-for-PTSD participant involved in a motor vehicle crash that caused her severe distress. She received one session of exposure therapy in the emergency department (ED) as part of an ongoing randomized controlled study examining the optimal dose of exposure therapy in the immediate aftermath of trauma. PTSD and depression measures were collected at pretreatment assessment and at 1- and 3-month follow-up. Potential PTSD biomarkers were also examined. Psychophysiological reactions were measured using skin conductance data during the exposure therapy session and the follow-up assessments. A fear-potentiated startle paradigm and a functional MRI (fMRI) behavioral inhibition task were used at follow-up. The participant demonstrated subjective and psychophysiological extinction from pre- to postimaginal exposure. At follow-up, she did not meet Diagnostic and Statistical Manual of Mental Disorders-IV (American Psychiatric Association, 2000) criteria for PTSD or demonstrate hyperarousal to trauma reminders, and showed robust fear extinction and the ability to inhibit responses in an fMRI behavioral inhibition task. In line with previous early intervention for the prevention of PTSD studies, this case report supports the need for ongoing empirical research investigating the possibility that one session of exposure therapy in the ED may attenuate risk for PTSD. Furthermore, the current findings demonstrate psychophysiological extinction serving as a prognostic indicator of treatment response for PTSD early intervention to be an avenue to explore in future systematic research.