Fibromyalgia syndrome (FM) represents a great challenge for clinicians and researchers because the efficacy of currently available treatments is limited. The present study examined the efficacy of Mindfulness-Based Stress Reduction (MBSR) for reducing functional impairment as well as the role of mindfulness-related constructs as mediators of treatment outcomes for people with FM. 225 participants with FM were randomized into three study arms: MBSR plus treatment-as-usual (TAU), FibroQoL (multicomponent intervention for FM) plus TAU, and TAU alone. The primary endpoint was functional impact (measured with the Fibromyalgia Impact Questionnaire Revised), and secondary outcomes included "fibromyalginess", anxiety and depression, pain catastrophising, perceived stress and cognitive dysfunction. The differences in outcomes between groups at post-treatment assessment (primary endpoint) and 12-month follow-up were analyzed using linear mixed-effects models and mediational models through path analyses. MBSR was superior to TAU both at post-treatment (large effect sizes) and at follow-up (medium to large effect sizes), and MBSR was also superior to FibroQoL post-treatment (medium to large effect sizes), but long-term it was only modestly better (significant differences only in pain catastrophising and fibromyalginess). Immediately post-treatment, the NNT for 20% improvement in MBSR versus TAU and FibroQoL was 4.0 (95%CI= 2.1-6.5) and 5.0 (95%CI= 2.7-37.3). An unreliable NNT value of 9 (not computable 95%CI) was found for FibroQoL vs. TAU. Changes produced by MBSR in functional impact were mediated by psychological inflexibility and the mindfulness facet Acting with awareness. These findings are discussed in relation to previous studies of psychological treatments for FM.