Objectives: A small but significant proportion of patients with peripheral neuropathic pain (NeP) are refractory to the typical treatments applied in clinical practice, including amitriptyline and gabapentin. Thus, they continue to suffer the debilitating effects of NeP. This study aimed to evaluate the cost-effectiveness of pregabalin in comparison to usual care, in patients with refractory NeP, from a third party payer's perspective (NHS). Methods: A stochastic simulation model was constructed, using clinical data from four non-randomized studies, to generate pain pathways of patients receiving usual care and pregabalin. Treatment effect (pain reduction) was converted to quality-of-life (QoL) data, using a regression analysis based on new utility data, collected from a survey of refractory NeP patients presenting to pain clinics in Cardiff, Wales. All relevant direct costs were estimated using resource use from the survey data (where available) and unit costs from the British National Formulary (BNF). The analysis was run over a 5-year time horizon, with costs and benefits discounted at 3.5%. Study limitations: The use of non-randomized (observational) data to characterize the effectiveness of treatments for NeP. Exclusion of productivity costs and consequences from the analysis. Results: In the base case analysis, an incremental cost-effectiveness ratio (ICER) of £10,803 per quality adjusted life year (QALY) was attained. This result was found to be reasonably insensitive to variations in the key input parameters, with ICERs ranging from £8505 to £22,845 per QALY gained. Conclusions: The analysis shows that pregabalin is a cost-effective alternative to usual care in patients with refractory NeP, with an ICER well below the threshold typically adopted by UK health technology assessment groups, such as NICE.