Objective: To evaluate the contribution of improvement in negative emotional cognitions, active cognitive coping, and control and chronicity beliefs to the outcome of multidisciplinary treatment in patients with chronic widespread pain. Design: Prospective cohort study. Patients: A total of 120 subjects diagnosed with chronic widespread pain, who completed a multidisciplinary pain programme. Methods: Data from baseline, 6 months and 18 months follow-up measurements were analysed. Longitudinal relationships were analysed between changes in cognitions and outcome, using generalized estimated equations. Outcome domains included: pain, interference of pain in daily life, depression, and global perceived effect. Cognitive domains included: negative emotional cognitions, active cognitive coping and control and chronicity beliefs. Results: Improvements in negative emotional cognitions were associated with improvements in all outcome domains, in particular with improvement in interference of pain with daily life and depression (between baseline and 6 months, and 6 and 18 months). Improvements in active cognitive coping were associated with improvements in interference of pain in daily life (between baseline and 6 months). Improvements in control and chronicity beliefs were associated with improvements in pain and depression (between 6 and 18 months). Conclusion: Improvement in negative emotional cognitions seems to be a key mechanism of change in multidisciplinary treatment of chronic widespread pain. Improvement in active cognitive coping and improvement in control and chronic timeline beliefs may also constitute mechanisms of change, although the evidence is less strong.Journal Compilation © 2014 Foundation of Rehabilitation Information.