Background: Mindfulness-based stress reduction (MBSR) proposes a systematic program for reduction of suffering associated with a wide range of medical conditions. Studies suggest improvements in general aspects of well-being, including quality of life (QoL), coping and positive affect, as well as decreased anxiety and depression. Methods: A quasi-experimental study examined effects of an 8-week MBSR intervention among 58 female patients with fibromyalgia (mean, 52 ± 8 years) who underwent MBSR or an active social support procedure. Participants were assigned to groups by date of entry, and 6 subjects dropped out during the study. Self-report measures were validated German inventories and included the following scales: visual analog pain, pain perception, coping with pain, a symptom checklist and QoL. Pre- and postintervention measurements were made. Additionally, a 3-year follow-up was carried out on a subgroup of 26 participants. Results: Pre- to postintervention analyses indicated MBSR to provide significantly greater benefits than the control intervention on most dimensions, including visual analog pain, QoL subscales, coping with pain, anxiety, depression and somatic complaints (Cohen d effect size, 0.40–1.10). Three-year follow-up analyses of MBSR participants indicated sustained benefits for these same measures (effect size, 0.50–0.65). Conclusions: Based upon a quasi-randomized trial and long-term observational follow-up, results indicate mindfulness intervention to be of potential long-term benefit for female fibromyalgia patients.