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BackgroundA recent randomized controlled trial provided preliminary evidence for the effectiveness of mindfulness based cognitive therapy (MBCT) for the top 10% frequent attenders in primary care with persistent medically unexplained symptoms (MUS). This qualitative study aims to explore working mechanisms and possible barriers of MBCT in this population. Methods Twelve participants of the trial were interviewed about their experiences. This was done before and after the MBCT course, and 12 months later. Written evaluations of participants and notes of participant observers were used for data-triangulation. Results In total, 35 qualitative interviews were conducted. MBCT initiated a process of change, starting with awareness of the present moment, the associated sensory experiences, thoughts and emotions and accepting rather than resisting these. Participants started to recognize their own behavioral patterns and change them, thus improving self-care. Self-compassion seemed to result from and facilitate this process. Main barriers were concurrent social problems and the inability or unwillingness to accept symptoms. Conclusions MBCT can start a process of change in patients with persistent MUS. Awareness and acceptance of painful symptoms and emotions are key factors in this process. Change of unhelpful behavioral patterns and increased self-care and self-compassion can result from this process.