Background: Patients with non-specific back pain are not a homogeneous group but heterogeneous with regard to their bio-psycho-social impairments. This study examined a sample of 173 highly disabled patients with chronic back pain to find out how the three subgroups based on the Multidimensional Pain Inventory (MPI) differed in their response to an inpatient pain management program. Methods: Subgroup classification was conducted by cluster analysis using MPI subscale scores at entry into the program. At program entry and at discharge after four weeks, participants completed the MPI, the MOS Short Form-36 (SF-36), the Hospital Anxiety and Depression Scale (HADS), and the Coping Strategies Questionnaire (CSQ). Pairwise analyses of the score changes of the mentioned outcomes of the three MPI subgroups were performed using the Mann-Whitney-U-test for significance. Results: Cluster analysis identified three MPI subgroups in this highly disabled sample: a dysfunctional, interpersonally distressed and an adaptive copers subgroup. The dysfunctional subgroup (29% of the sample) showed the highest level of depression in SF-36 mental health (33.4 +/- 13.9), the interpersonally distressed subgroup (35% of the sample) a modest level of depression (46.8 +/- 20.4), and the adaptive copers subgroup (32% of the sample) the lowest level of depression (57.8 +/- 19.1). Significant differences in pain reduction and improvement of mental health and coping were observed across the three MPI subgroups, i.e. the effect sizes for MPI pain reduction were: 0.84 (0.44 - 1.24) for the dysfunctional subgroup, 1.22 (0.86 - 1.58) for the adaptive copers subgroup, and 0.53 (0.24 - 0.81) for the interpersonally distressed subgroup (p = 0.006 for pairwise comparison). Significant score changes between subgroups concerning activities and physical functioning could not be identified. Conclusions: MPI subgroup classification showed significant differences in score changes for pain, mental health and coping. These findings underscore the importance of assessing individual differences to understand how patients adjust to chronic back pain.