Background Physiological reactivity to trauma‐related cues is a primary symptom of PTSD and can be assessed objectively using script‐driven imagery paradigms. However, subjective self‐reported symptom measures are the most common outcome indices utilized in PTSD treatment trials and clinic settings. We examined physiological reactivity during a short trauma imagery task as an objective index of response to PTSD treatment, optimized for use in routine clinical care settings. Methods Participants were 35 male combat veterans receiving prolonged exposure (PE) therapy in a Veterans Affairs outpatient clinic. In addition to traditional subjective self‐reported and clinician‐rated symptom measures, patients also completed a script‐driven imagery task in which heart rate (HR) and skin conductance (SC) were recorded at three assessment points across treatment. We examined changes in subjective symptom measures and objective trauma‐specific physiological reactivity over the course of PE, and investigated the association between pretreatment physiological reactivity and treatment response. Results Patients who completed PE showed significantly diminished HR and SC reactivity to trauma imagery across therapy. Additionally, individuals showing greater trauma‐specific HR reactivity at pretreatment showed greater reductions in subjectively reported PTSD symptoms after the first session of imaginal exposure, and at posttreatment. Conclusions Findings support the utility of physiological reactivity during trauma imagery as an objective outcome measure that has the potential to be incorporated into evidence‐based PTSD treatment in routine clinical settings, or prospective studies related to the individualization of care at pretreatment.