OBJECTIVES: Failed back surgery syndrome (FBSS) represents one main cause of chronic neuropathic or mixed pain and functional disability. Results from previous clinical trials and from the PRECISE naturalistic study [Zucco et al, Neuromodulation, 2015] show that Spinal Cord Stimulation (SCS) provides pain relief and improves patients’ health. Our current aim is to understand the relationship between pain intensity, functional disability, and overall Health-Related Quality-of-life (HRQoL). METHODS: At recruitment (before SCS) and every 6 months for 2 years after SCS a battery of questionnaires/tests were completed: EQ-5D-3L and SF-36 for HRQoL, the Numerical Rating Scale (NRS) to measure pain intensity, and the Oswestry Disability Index (ODI) to measure disability/functional capability. Statistical tests were conducted to compare the HRQoL levels (using the EQ-5D utility index, the EQ-VAS, the SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) index), NRS and ODI at baseline with those measured during the observational period. Multilevel regression analyses were conducted to investigate the association between the HRQOL indexes and the NRS and ODI indexes, on adjusting for: age, gender, previous surgery, education, baseline level of the dependent variable, and time of assessment. RESULTS: Eighty patients (40% male, mean age=58 years) participated. Significant improvements (p<0.001) in pain intensity, functional capability and HRQoL were reached after 6 months from SCS and maintained or further improved until the end of the observational period. According to the regression models, every HRQoL index was significantly associated (p<0.001) with both the NRS and the ODI indexes at any time of assessment. CONCLUSIONS: Our results suggest that in a 2-year observational period, SCS+CMM treatment reduces significantly pain intensity and functional disability in patients with FBSS, with significant repercussions on their general HRQOL. Furthermore, our results suggest the HRQoL instruments used in this study are valid to assess overall patients’ health and treatment outcomes.