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Background. Illness perceptions have been shown to predict patient activities. Therefore, studies of the effectiveness of a targeted illness-perception intervention on chronic nonspecific low back pain (CLBP) are needed. Objective. The purpose of this study was to compare the effectiveness of treatment of illness perceptions against a waiting list for patients with CLBP. Design. This was a prospectively registered randomized controlled trial with an assessor blinded for group allocation. Setting. The study was conducted in an outpatient rehabilitation clinic. Participants. The participants were 156 patients (18-70 years of age) with CLBP (>3 months). Intervention. Patients were randomly assigned to either a treatment group or to a waiting list (control) group. Trained physical therapists and occupational therapists delivered 10 to 14 one-hour treatment sessions according to the treatment protocol. Measurements. The primary outcome measure was change in patient-relevant physical activities (Patient-Specific Complaints questionnaire). The secondary outcome measures were changes in illness perceptions (Illness Perceptions Questionnaire) and generic physical activity level (Quebec Back Pain Disability Scale). Measurements were taken at baseline (0 weeks) and after treatment (18 weeks). Results. A baseline-adjusted analysis of covariance showed that there were statistically significant differences between intervention and control groups at 18 weeks for the change in patient-relevant physical activities. This was a clinically relevant change (19.1 mm) for the intervention group. Statistically significant differences were found for the majority of illness perception scales. There were no significant differences in generic physical activity levels. Limitations. Longer-term effectiveness was not studied. Conclusions. This first trial evaluating cognitive treatment of illness perceptions concerning CLBP showed statistically significant and clinically relevant improvements in patient-relevant physical activities at 18 weeks., Chronic nonspecific low back pain (CLBP) is a major cause of activity limitations, absenteeism, and high health care expenses. (1) The prevalence of CLBP is estimated at approximately 23%, and [...]