Despite availability of effective trauma-focused psychotherapies, treatment non-response in youth with (partial) posttraumatic stress disorder remains substantial. Studies in adult PTSD have suggested that cortisol is associated with treatment outcome. Furthermore, cortisol prior to treatment could be used to predict treatment success. However, there is a lack of comparable studies in youth with (partial) PTSD. The objective of the current study was therefore to test whether cortisol prior to treatment would differ between treatment responders and non-responders and would positively predict the extent of clinical improvement in youth with (partial) PTSD. Youth aged 8-18 with PTSD (79.2%) or partial PTSD (20.8%) were treated with 8 sessions of either trauma-focused cognitive behavioral therapy (TF-CBT) or eye movement desensitization and reprocessing (EMDR). Prior to treatment initiation, salivary cortisol was measured in treatment responders (n = 23) and treatment non-responders (n = 30) at 10 and 1 min before and 10, 20 and 30 min after personalized trauma script driven imagery (SDI). The cortisol stress response (>1.5 nmol/L increase from baseline) and basal cortisol secretion was assessed during the SDI procedure. We hypothesized that treatment responders would display higher cortisol levels caused by increased cortisol reactivity prior to trauma-focused psychotherapy relative to psychotherapy non-responders and higher cortisol levels would positively predict the extent of clinical improvement. Script driven imagery did not induce a cortisol stress response in all but two participants. Prior to treatment responders showed significantly higher basal cortisol secretion during SDI compared to treatment non-responders. This effect remained significant after controlling for gender. Higher pre-treatment basal cortisol secretion further positively predicted the extent of clinical improvement during trauma-focused psychotherapy. Because SDI failed to provoke a cortisol stress response in our sample, the question if cortisol reactivity differs between treatment responders and non-responders remains inconclusive. However, our results do suggest that higher pretreatment basal cortisol secretion forms a potential indicator of prospective trauma-focused psychotherapy response in youth with (partial) PTSD. Although, the amount of uniquely explained variance in clinical improvement by pre-treatment cortisol secretion is limited and still renders insufficient basis for clinical applicability, these findings do suggest directions for future studies to delineate the mechanisms of treatment success in youth with (partial) PTSD. Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.