For many decades, the U.S. military's general operational guideline has been to limit the use of trauma-focused treatments for combat and operational stress reactions in military service members until they have returned from deployment. Recently, published clinical trials have documented that active-duty military personnel with combat-related posttraumatic stress disorder (PTSD) can be treated effectively in garrison. However, there are limited data on the treatment of combat and operational stress reactions or combat-related PTSD during military deployments. This prospective, nonrandomized trial evaluated the treatment of active-duty service members (N = 12) with combat and operational stress reactions or combat-related PTSD while deployed to Afghanistan or Iraq. Service members were treated by deployed military behavioral health providers using modified Prolonged Exposure (PE; n = 6) or modified Cognitive Processing Therapy (CPT; n = 6), with protocol modifications tailored to individual mission requirements. The PTSD Checklist-Military Version (PCL-M) total score was the primary outcome measure. Results indicated that both groups demonstrated clinically significant change in PTSD symptoms as indicated by a reduction of 10 points or greater on the PCL-M. Participants treated with modified PE had significant reductions in PTSD symptoms, t = -3.83, p = .01; g = -1.32, with a mean reduction of 18.17 points on the PCL-M. Participants treated with modified CPT had a mean PCL-M reduction of 10.00 points, but these reductions were not statistically significant, t = -1.49, p = .12; g = -0.51. These findings provide preliminary evidence that modified forms of PE and CPT can be implemented in deployed settings for the treatment of combat and operational stress reactions and combat-related PTSD.