The glutamatergic N-methyl-D-aspartate receptor antagonist ketamine produces transient dissociative states and alters cognitive functioning in healthy humans, thus resembling the core symptoms of acute and chronic post-traumatic stress disorder (PTSD). First evidence exists that the common use of the analgesic and sedative properties of ketamine during emergency care correlates with sustained symptoms of PTSD in accident victims. The aim of the present study was to examine whether ketamine administration after moderate accidental trauma modulates dissociation and other symptoms of acute stress disorder (ASD) in the direct aftermath of the event. Accident victims were screened within the third day after admission to hospital for symptoms of ASD (Peritraumatic Dissociative Experiences Questionnaire, ASD Scale) and prior stressful life events (Traumatic Life Events Questionnaire). Subjects had received a single or fractionated dose of either racemic ketamine (n = 13), opioids (n = 24) or non-opioid analgesics (n = 13) during initial emergency treatment. There were no significant differences between medication groups in demographic and clinical characteristics such as injury severity or prior traumatization. With respect to ASD symptomatology three days post-event there were significant associations between ketamine analgosedation and increased symptoms of dissociation, reexperiencing, hyperarousal and avoidance relative to the comparison groups.Growing evidence exists that ketamine might modulate or aggravate early post-traumatic stress reactions when given in the acute trauma phase, which in turn might contribute to long-lasting symptomatology.