Recently a clinical prediction rule (CPR) for lumbar regional spinal thrust manipulation (STM) has shown predictive success in patients with back pain who met specific selection criteria. The purpose of this study was to compare the effectiveness of STM and mechanical diagnosis and therapy (MDT) in patients who are positive for the STM CPR. Following initial examination, 31 participants were randomized to the STM group (n = 16) and to the MDT group (n = 15). Two weeks following initial examination, four participants chose to cross over from the STM group to the MDT group. The Oswestry Disability Index (ODI), Fear-Avoidance Beliefs Questionnaire work subscale (FABQw), and the Numerical Pain Rating Scale (NPRS) were administered initially, and at 2-weeks and 4 week follow-up (discharge). Data were analyzed to determine changes in ODI and NPRS scores from initial examination through one month. Of the 31 participants, one patient who met only three of five selection criteria and four others who chose to switch groups were removed from the analysis. Both groups exhibited statistically significant improvements in ODI and NPRS scores from baseline to final visit but there was no significant difference in scores between groups at 4 weeks. In this sample of patients, the selection criteria for this CPR were not exclusive for lumbopelvic STM. Mechanical diagnosis and therapy was an equally viable choice for these patients.