Recent studies suggest that mixed-handedness is a risk factor for posttraumatic stress disorder (PTSD). This study examined whether mixed-handed veterans with combat-related PTSD respond more poorly to psychosocial treatment. Consistency of hand preference was assessed in 150 Vietnam combat veterans with PTSD using the Edinburgh Handedness Inventory (R. C. Oldfield, 1971). Growth modeling analyses using Mplus (L. K. Muthén & B. Muthén, 2002) identified that PTSD veterans with mixed-handedness reported significantly less treatment improvement on the PTSD Checklist (F. W. Weathers, B. T. Litz, D. S. Herman, J. A. Huska, & T. M. Keane, 1993) than did veterans with consistent handedness. These data suggest that mixed-handedness is associated with poorer PTSD treatment response. Several possible explanations for this finding are discussed.