OBJECTIVES:  To explore the relationship between health-related quality of life (HRQL) and response to treatment in people with moderate-to-severe, chronic, lower back pain treated with WHO-step III opioids. METHODS:  A prospective, 12-week, random-select, open-label, blinded end-point (PROBE) study was carried out in 88 medical centres in Germany. 453 people requiring pain treatment with a WHO-step III opioid received treatment with morphine, oxycodone, or oxycodone/naloxone. HRQL was assessed using several tools, including the EQ-5D index score. Response to treatment and EQ-5D over time were analysed. Response was defined as a lack of premature study discontinuation; a bowel function index worsening of ≤50% versus baseline; and an improvement of ≥50% versus baseline with respect to low back pain intensity index, pain-related disabilities in daily life and quality of life. The definition was selected to reflect assessment of response in clinical practice, in which tolerability and analgesic efficacy are typically considered in combination. RESULTS:  32/144 (22.2%) of people treated with oxycodone/naloxone responded to treatment, compared with 14/151 (9.3%) and 10/158 (6.3%) who received oxycodone and morphine, respectively. The difference was statistically significant (p<0.001). Mean EQ-5D at baseline was estimated to be 0.39 (95% confidence interval [CI] 0.36, 0.41). Responders to treatment reported an average EQ-5D of 0.78 (95% CI 0.71, 0.85) at 12 weeks. By contrast, people who did not respond to treatment on the grounds of both tolerability and analgesic efficacy reported an average EQ-5D of 0.68 (95% CI, 0.64, 0.71). CONCLUSIONS:  Results of this analysis demonstrate that there is an important difference in mean HRQL between people who respond well to treatment for chronic pain, versus those who have less pain relief and who suffer worsening constipation. Decision analytic modelling using these data will be supportive for newer therapies which demonstrate both improved efficacy and reduced impact upon bowel functioning.