Abstract: d-Cycloserine (DCS) is a partial NMDA receptor agonist that has been shown to enhance therapeutic response to exposure-based treatments for anxiety disorders, but has not been tested in the treatment of combat-related posttraumatic stress disorder (PTSD). The aim of this randomized, double-blind, placebo-controlled trial was to determine whether DCS augments exposure therapy for PTSD in veterans returning from Iraq and Afghanistan and to test whether a brief six-session course of exposure therapy could effectively reduce PTSD symptoms in returning veterans. In contrast to previous trials using DCS to enhance exposure therapy, results indicated that veterans in the exposure therapy plus DCS condition experienced significantly less symptom reduction than those in the exposure therapy plus placebo condition over the course of the treatment. Possible reasons for why DCS was associated with poorer outcome are discussed.Clinicaltrials.gov Registry #: NCT00371176; A Placebo-Controlled Trail of d-Cycloserine and Exposure Therapy for Combat-PTSD; www.clinicaltrials.gov/ct2/results?term=NCT00371176.