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Objective: Mindfulness-based cognitive therapy (MBCT) has recently been proposed as a treatment option for chronic depression. The cognitive behavioral analysis system of psychotherapy (CBASP) is the only approach specifically developed to date for the treatment of chronically depressed patients. The efficacy of MBCT plus treatment-as-usual (TAU), and CBASP (group version) plus TAU, was compared to TAU alone in a prospective, bicenter, randomized controlled trial. Method: One hundred and six patients with a current DSM–IV defined major depressive episode and persistent depressive symptoms for more than 2 years were randomized to TAU only (N = 35), or to TAU with additional 8-week group therapy of either 8 sessions of MBCT (n = 36) or CBASP (n = 35). The primary outcome measure was the Hamilton Depression Rating Scale (24-item HAM-D, Hamilton, 1967) at the end of treatment. Secondary outcome measures were the Beck Depression Inventory (BDI; Beck, Steer, & Brown, 1996) and measures of social functioning and quality of life. Results: In the overall sample as well as at 1 treatment site, MBCT was no more effective than TAU in reducing depressive symptoms, although it was significantly superior to TAU at the other treatment site. CBASP was significantly more effective than TAU in reducing depressive symptoms in the overall sample and at both treatment sites. Both treatments had only small to medium effects on social functioning and quality of life. Conclusions: Further studies should inquire whether the superiority of CBASP in this trial might be explained by the more active, problem-solving, and interpersonal focus of CBASP.