OBJECTIVES: Estimate the cost-effectiveness (CE) of Pregabalin (PGB) and Usual Care (UC) in refractory out-patients with pDPN treated in usual medical practice in Primary Care settings in Spain. METHODS: Data extracted from a 12-week non-interventional study were used in the CE analysis. Previously, PGB naïve patients treated with UC or PGB, matched by age (+5years), sex and pain intensity (+5pts), refractory (≥40VAS-MPQ) to previous treatment were selected. Patients could switch to PGB (monotherapy/add-on) or to UC other than PGB. Time horizon was 12 weeks. Effectiveness was expressed as quality-adjusted life years (QALY) gain. The CEA included the perspectives of the NHS and society (2006), with results expressed as incremental cost effectiveness ratio (ICER). Bootstrapping techniques (10,000 re-samples) were used to obtain the probabilistic ICER, its 95% percentile confidence interval (CI) and the CE acceptability curve. Univariate probabilistic sensitivity analysis was also performed. RESULTS: A total of 189 patients, 112 in PGB group and 77 in UC were identified. Compared with UC, PGB was associated with higher QALY gain; 0.0406±0.0343 versus 0.0285±0.0350 (p=0.598). Although drug costs were higher for PGB (€262±132 vs. €66±66, p<0.001), overall total costs (€1,368±1,229 vs. €1,258±1,474; p=0.587), or health care costs (€628±590 vs. €469±420; p=0.134) were similar, although due its observational design and small sample size, ICERs varied extensively from €5302 (95% CI: dominant; €144,105) for total costs to €14,381 (dominant; €115,648) for health care costs and €39,592 (dominant; €131,754) for drug costs. However, probabilistic analyses showed 79% to 84% of ICERs were below the threshold of €30,000/QALY. CONCLUSIONS: This study suggests that using PGB to treat refractory out-patients with pDPN in community medical practice in Spain is cost-effective compared to UC in majority of patients. It also highlights the burden of the disease and supports the availability of effective treatments available for patients not achieving pain relief from older therapies.