BACKGROUND: Failed back surgery syndrome (FBSS) represents one main cause of chronic neuropathic or mixed pain, functional disability and reduced Health Related Quality of Life (HRQoL). Spinal Cord Stimulation (SCS) can be a value for money option to treat patients refractory to conventional medical management (CMM). We estimated from real-world data: 1) the amount of reduced levels of HRQoL of target patients compared to general population, 2) the relationship between pain intensity, functional disability, and overall HRQoL, and 3) the improvement of patients’ health from SCS intervention, and 4) we give some insights and make some suggestions on the selection of a battery of patients’ reported health instruments for use in routine clinical practice. METHODS: At recruitment (before SCS) and every 6 months for 2 years after SCS a battery of questionnaires/tests were completed: the generic EQ-5D and SF-36 for HRQoL, the specific Numerical Rating Scale (NRS) to measure pain intensity, and Oswestry Disability Index (ODI) to measure functional disability. We conducted multilevel regression analyses to investigate the association of HRQoL with the NRS and ODI indexes; multiple regression analyses to compare EQ-5D data with those of the general population adjusted for age, sex and education, and statistical tests to compare the changes of HRQoL, NRS and ODI estimates at baseline with those measured during the follow-up. RESULTS: Eighty patients (40% male, mean age = 58 years) participated. HRQoL was significantly worse in the patients than in the corresponding general population. Pain, functional disability and HRQoL significantly related each other during follow-up, Significant improvements (p < 0.001) in pain intensity, functional capability and HRQoL were reached after 6 months from SCS and generally remained stable during follow-up. Specific instruments provided detailed information on disability and pain, while generic instruments assessed the overall HRQoL and allowed a comparison with the general population’s one. CONCLUSIONS: SCS + CMM treatment reaches a statistically significant and probably a clinically relevant improvement in pain perception, functional disability and HRQoL in patients with FBSS refractory to CMM. An appropriate selection of instruments for use in clinical practice is crucial for a routine assessment of health perception in patients, aimed to guide decisions for optimal treatment.