OBJECTIVES: To compare the health care costs 6 months prior to and 6 months after initiation of pregabalin in difficult-to-treat neuropathic pain (NeP) patients. METHODS: This was a retrospective longitudinal database study in NeP patients from the South-West region of Sweden (1.5 million inhabitants). Individual patient data from the 1st of January 2000 on health care visits (outpatient, inpatient, primary care), costs, mortality and diagnoses were included. Data from the Swedish Prescribed Drug register were included from July 1, 2005 until December 31, 2007. Difficult-to-treat NeP was defined as patients with a NeP diagnosis in 2006, who had had 2 prescriptions of at least three pain medications during one year from the index diagnosis date. The patients should also have had two or more prescriptions of pregabalin preceded by at least a six months pregabalin naïve period.   RESULTS: A total of 462 difficult-to-treat NeP patients met the above criteria and were included in the analyses. There was a statistically significant reduction in NeP related costs (visits registered with a NeP diagnosis) after initiation of pregabalin (p=0.0042 Mann-Whitney). The mean per patient NeP related costs were SEK17,684 (€1,845) 6 months before and SEK10,642 (€1,110) 6 months after pregabalin initiation. The mean non-NeP related costs before treatment (SEK46,095; €4,809) did not differ significantly from the non-NeP costs after treatment (SEK 51,632; €5,387), p=0.8016. The number of NeP-related in-patient visits, primary care visits and the number of days in hospital decreased significantly (p = 0.0475, p = 0.0129, p = 0.0179, respectively) after treatment with pregabalin. CONCLUSIONS: Initiation of pregabalin significantly reduced the NeP related health care costs in the 6-month period following initiation. Of note was the non significant difference in non-NeP related costs, probably reflecting the on-going costs associated with management of the patients’ concurrent conditions, eg, diabetes.