BACKGROUND: Spinal Manipulative Therapy (SMT) and Active Exercise Therapy (AET) have both demonstrated efficacy in the treatment of Chronic Lower Back Pain (CLBP). A Clinical Prediction Rule (CPR) for responsiveness to SMT has been validated in a heterogeneous lower back pain population; however there is a need to evaluate this CPR specifically for patients with CLBP, which is a significant source of disability. METHODS: We conducted a randomized controlled trial (RCT) in Veteran Affairs and civilian outpatient clinics evaluating a modification of the original CPR (mCPR) in CLBP, eliminating acute low back pain and altering the specific types of SMT to improve generalizability. We enrolled and followed 181 patients with CLBP from 2007 to 2010. Patients were randomized by status on the mCPR to undergo either SMT or AET twice a week for four weeks. Providers and statisticians were blinded as to mCPR status. We collected outcome measures at 5, 12 and 24-weeks post baseline. We tested our study hypotheses by a general linear model repeated measures procedure following a univariate analysis of covariance approach. Outcome measures included, Visual Analogue Scale, Bodily pain subscale of SF-36 and the Oswestry Disability Index, Patient Satisfaction and Patient Expectation. RESULTS: Of the 89 AET patients, 69 (78%) completed the study and of the 92 SMT patients, 76 (83%) completed the study. As hypothesized, we found main effects of time where the SMT and AET groups showed significant improvements in pain and disability from baseline. There were no differences in treatment outcomes between groups in response to the treatment, given the lack of significant treatment x time interactions. The mCPR x treatment x time interactions were not significant. The differences in outcomes between treatment groups were the same for positive and negative on the mCPR groups, thus our second hypothesis was not supported. CONCLUSIONS: We found no evidence that a modification of the original CPR can be used to discriminate CLBP patients that would benefit more from SMT. Further studies are needed to further clarify the patient characteristics that moderate treatment responsiveness to specific interventions for CLBP. TRIAL REGISTRATION: ISRCTN30511490.