High rates of drop-out from treatment of PTSD have challenged implementation. Care models that integrate PTSD focused psychotherapy and complementary interventions may provide benefit in retention and outcome. The first 80 veterans with chronic PTSD enrolled in a 2-week intensive outpatient program combining Prolonged Exposure (PE) and complementary interventions completed symptom and biological measures at baseline and posttreatment. We examined trajectories of symptom change, mediating and moderating effects of a range of patient characteristics. Of the 80 veterans, 77 completed (96.3%) treatment and pre- and posttreatment measures. Self-reported PTSD (p < .001), depression (p < .001) and neurological symptoms (p < .001) showed large reductions with treatment. For PTSD, 77% (n = 59) showed clinically significant reductions. Satisfaction with social function (p < .001) significantly increased. Black veterans and those with a primary military sexual trauma (MST) reported higher baseline severity than white or primary combat trauma veterans respectively but did not differ in their trajectories of treatment change. Greater cortisol response to the trauma potentiated startle paradigm at baseline predicted smaller reductions in PTSD over treatment while greater reductions in this response from baseline to post were associated with better outcomes. Intensive outpatient prolonged exposure combined with complementary interventions shows excellent retention and large, clinically significant reduction in PTSD and related symptoms in two weeks. This model of care is robust to complex presentations of patients with varying demographics and symptom presentations at baseline. (PsycInfo Database Record (c) 2021 APA, all rights reserved).