OBJECTIVES: Failed back surgery syndrome (FBSS) represents one main cause of chronic neuropathic or mixed pain. Clinical trials have shown that Spinal Cord Stimulation (SCS) provides pain relief and improves patients’ health. We assessed in a naturalistic context the cost-utility of SCS in FBSS patients unresponsive to conventional medical management (CMM). METHODS: We conducted an observational, multicenter, longitudinal prospective study in which a sample of patients assigned to receive SCS in addition to CMM was observed for 24 months after the intervention. We collected before and after undergoing SCS the following data: direct and indirect costs, adopting the National Health Service (NHS) and the societal perspectives, pain status, using the Numerical Rating Scale (NRS, scoring from 0 (no pain) to 10 (maximum pain)), and HRQoL, using the SF-36 and EQ-5D. Costs and benefits pre-SCS versus post-SCS were compared to estimate the incremental cost-effectiveness and the cost-utility ratios. The following results focus on the cost/QALY ratio. RESULTS: Eighty patients (40% male, mean age 58 years) were recruited. Significant improvements in pain intensity and HRQoL were reached after 6 months from SCS and maintained or further improved until the end of the observational period. In particular, after 24 months from SCS the mean NRS significantly decreased (p<0.01) from 7.6 to 5.1, and the mean EQ-5D-utility significantly (p<0.01) increased from 0.07 to 0.40. The ICUR was equal to 27,519€/QALY, according to the NHS perspective. The cost-utility acceptability curve shows that if decision makers’ willingness-to-pay per QALY was 45,000€, then SCS implantation would be cost effective in 97% and 99% of cases, according to the societal and NHS perspectives, respectively. CONCLUSIONS: In a 2-year observational period, SCS+CMM treatment of FBSS patients increases medical direct costs but allows to improve significantly patients’ clinical health and HRQoL, resulting in a cost/QALY ratio largely lower than the commonly accepted willingness-to-pay threshold.