Patients with co-morbid chronic pain and post-traumatic stress disorder (PTSD) pose significant treatment challenges. This study evaluated the effectiveness of an interdisciplinary pain rehabilitation program (IPRP) in improving pain and PTSD outcomes, as well as reducing medication use. In addition, the mediating effect of pain catastrophizing, which is theorized to underlie the pain and PTSD comorbidity, was examined. Participants included 83 completers of an IPRP with chronic pain and a provisional PTSD diagnosis. Significant improvements were found for pain outcomes, PTSD symptomatology, depressive symptoms, physical performance, and medication use (i.e., opioids and benzodiazepines). At discharge, 86.7% of participants reliably improved in at least one key measure of functioning and 50.6% demonstrated reliable improvement in PTSD symptomatology. Change in pain catastrophizing mediated improvements in pain interference and PTSD symptomatology. Results support the potential utility of an interdisciplinary pain treatment approach in the treatment of patients with comorbid pain and PTSD.