BACKGROUND: This study aimed: (a) to examine the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) for patients with a treatment-refractory anxiety disorders compared to Relapse Prevention-Cognitive Behavioral Therapy (CBT-RP); and (b) to explore candidate mediating variables. METHODS: We conducted a pragmatic randomized controlled trial comparing MBCT with CBT-RP in a group format for 136 outpatients with treatment-refractory DSM-IV defined anxiety disorder, who insufficiently responded to first-line psychological treatment. RESULTS: At post-treatment, the MBCT group showed a significantly larger decrease in self-reported anxiety (Beck Anxiety Inventory), avoidance (Fear Questionnaire), difficulties in emotion regulation (Difficulties in Emotion Regulation Strategies), and worry (Penn State Worry Questionnaire), as well as a significantly larger increase in mindfulness skills (Five Facet Mindfulness Questionnaire). After a 6-month follow-up treatment gains were somewhat diminished. Effects of MBCT on anxiety at post-treatment did not prove to be mediated by mindfulness skills, difficulties in emotion regulation strategies, worry, or rumination (Rumination on Sadness Scales) at mid-treatment. CONCLUSIONS: MBCT seems to be a promising intervention in routine clinical care for persons with an anxiety disorder who insufficiently responded to first-line psychological treatment. Future research in larger samples assessing long-term effects and using intensive longitudinal designs to identify possible working mechanisms is called for.