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To evaluate the effect on disability, kinesiophobia, pain, and the quality of life of a long-lasting multidisciplinary program based on cognitive-behavioral therapy and targeted against fear-avoidance beliefs in patients with chronic low back pain.Study design: parallel-group, randomized, superiority controlled study. Ninety patients were randomly assigned to a multidisciplinary program consisting of cognitive-behavior therapy and exercise training (experimental group, 45 patients) or exercise training alone (control group, 45 patients). Before treatment (T1), 5 weeks later (instructive phase, T2), and 12 (posttreatment analysis, T3) and 24 months after the end of the instructive phase (1-year follow-up, T4), all of the patients completed a booklet containing the Roland-Morris Disability Questionnaire Scale (primary outcome), the Tampa Scale for Kinesiophobia, a pain numerical rating scale, and the Short-Form Health Survey. A linear mixed model for repeated measures was used to analyze each outcome measure, and the reliable change index/clinically significant change method was used to assess the clinical significance of the changes.The linear mixed model analysis showed a remarkable group, time, and interaction effect for group * time in all of the primary and secondary outcomes (P always <0.001). The majority of the patients in the experimental group achieved a reliable and clinically significant improvement, whereas the majority of those in the control group experienced no change.The long-lasting multidisciplinary program was superior to the exercise program in reducing disability, fear-avoidance beliefs and pain, and enhancing the quality of life of patients with chronic low back pain. The effects were clinically tangible and lasted for at least 1 year after the intervention ended.