Background: Negative post-traumatic cognitions (PTC) are a risk factor for the development and maintenance of post-traumatic stress disorder (PTSD). PTC have further been linked to symptoms of depression, anxiety, and emotion regulation (ER). We investigated the role of PTC in the treatment of PTSD patients. Method: We analyzed data from 339 inpatients (279 female) who received inpatient trauma-focused treatment for eight to twelve weeks. PTC, symptoms of PTSD, depression, anxiety, and ER were assessed at admission and discharge. PTC assessment included negative cognitions about the self, the world, and self-blame. Results: The results show that all symptoms and ER, and all PTC except for self-blame, decreased during treatment. Only baseline level of PTC about the self was related to changes in depression severity. The other baseline levels of PTC were not related to any changes in symptom severity. Changes in PTC about the self were related to changes in all symptoms and ER. Changes in PTC about the world were only linked to symptoms of PTSD. Changes in self-blame were only associated with symptoms of re-experiencing. Conclusions: Our findings suggest that PTC about the self play a more general and PTC about the world a more specific role in the treatment of PTSD. Further research is needed to clarify the role of self-blame in the treatment.