Context Two sets of findings predict smaller cerebral cortical gray matter volume in adult posttraumatic stress disorder (PTSD). Measures of intracranial tissue volume and cerebral tissue volume have been observed to be smaller in adolescents with maltreatment-related PTSD. Second, lower intelligence, a risk factor for PTSD, is associated with smaller cerebral tissue volumes. Nevertheless, to our knowledge, only 1 study has observed globally smaller cerebral tissue volume in adults with PTSD. Objectives To apply a recently developed method providing improved estimates of cortical volume and to estimate associations between adult PTSD and selected regional cortical volumes not yet investigated. Design Between-group comparison of global and regional cerebral cortical volumes in adult patients with combat-related PTSD and controls. Setting Two Department of Veterans Affairs medical centers with large inpatient and outpatient PTSD catchments. Participants Ninety-seven combat-exposed veterans of the Vietnam and Persian Gulf wars. Main Outcome Measure Global and regional cortical volumes determined using the FreeSurfer software program and the Desikan et al parcellation (modified). Results Cerebral cortical volume, thickness, and area were observed to be smaller in association with adult combat-related PTSD. Robust associations were observed between PTSD and smaller cortical volumes in the parahippocampal gyrus, superior temporal cortex, lateral orbital frontal cortex, and pars orbitalis of the inferior frontal gyrus. Conclusions Cerebral cortical volume, thickness, and area may be smaller in adult chronic severe PTSD; however, the extracted structural variables did not mediate relations between intelligence and PTSD. The 4 regions exhibiting especially smaller cortical volumes in this sample share involvement in mechanisms subserving "top-down" facilitation of the identification of objects and words. Compromise of these regions may result in difficulty in relearning pretrauma schemata for interpreting the civilian physical and social environments.