Background: Emotional disorders are highly prevalent in primary care. Transdiagnostic cognitive behavior therapy (TD-CBT) is a promising treatment of emotional disorders. In this study, we evaluated several emotion regulation strategies as potential mediators of treatment outcomes in a clinical sample of primary care. Methods: A total of 1061 primary care patients were included in a randomized clinical trial comparing treatment- as-usual (TAU) to TD-CBT+TAU. Of these, 631 (TAU=316; TD-CBT+TAU=315) completed the full treatment and all pre- and post-treatment scales to assess symptoms (anxiety, depression, somatization), emotion regulation strategies (worry, rumination, negative metacognition, suppression, cognitive reappraisal), overall functioning, and quality of life (QoL). Results: Treatment and direct effects showed that TD-CBT+TAU was superior to TAU alone. On the multivariate mediation analysis of indirect effects, three maladaptive strategies (worry, rumination and negative metacognition) had significant effects on all emotional symptoms. Suppression was also significant for depression. Rumination and negative metacognition were significant mediators of functioning, while only negative meta- cognition was significant for QoL. Reappraisal had no effect on any outcome. Limitations: We focused mainly on maladaptive cognitive emotion regulation strategies and only studied one behavioural strategy (suppression) and one adaptive strategy (reappraisal). Conclusions: Targeting certain maladaptive emotion regulation strategies (worry, rumination, suppression, negative metacognition) as mediators for treatment with TD-CBT could reduce emotional symptoms and improve well-being. Negative metacognition was the most transdiagnostic strategy, whereas an adaptive strategy such as reappraisal was not a mediator. Thus, maladaptive emotion regulation strategies are key mediators in transdiagnostic therapy for emotional disorders in primary care.