Exposure to traumatic events and posttraumatic stress disorder (PTSD) are common among individuals with substance use disorders (SUDs). Although the presence of trauma exposure and/or PTSD among those with SUDs is associated with a range of negative outcomes, much remains to be understood about the factors contributing to these outcomes. Anxiety sensitivity (the tendency to respond fearfully to the signs and symptoms of anxiety) has been linked to greater PTSD symptoms and the use of substances to cope with PTSD symptoms, and is a promising factor for understanding the negative outcomes associated with co-occurring PTSD and SUDs. This study examined the association between anxiety sensitivity and trauma cue reactivity among 194 trauma-exposed patients with SUDs (27.3% met criteria for current PTSD). Participants completed ratings of negative affect and substance cravings prior to and after exposure to a personally-relevant trauma cue. Results indicated that anxiety sensitivity was associated with greater emotional reactivity (but not craving reactivity) to the trauma cue; neither PTSD symptom severity nor PTSD diagnosis moderated these associations. PTSD symptom severity was associated with greater emotional and craving reactivity to the trauma cue. Results highlight the potential utility of targeting anxiety sensitivity in treatments for trauma-exposed patients with SUDs with and without PTSD.