OBJECTIVES: To analyze the Pregabalin (PGB) effect under routine medical practice on longitudinal health and non-health resources utilization (HRU) and derived costs of treating refractory painful Radiculopathy in Primary Care Setting (PCS) during 12-weeks. METHODS: A representative sample of PC centres included men and women above 18 years, with chronic pain (6-month or more) due to cervical (17%) or lumbar (83%) radiculopathy refractory to, at least, one previous analgesic [mean (SD) number of drugs; 2.6 (1.4)], in a prospective, naturalistic, 12-weeks two-visit study. Health resources included all-type medical visits, hospitalizations, complementary test and pharmacological and non-pharmacological therapies. Non-health included wages loses due to loss-work-days equivalents (LWDE= absenteeism days + days working with reduced productivity due to pain). Pain severity was measured by McGill-pain scale. Descriptive statistics and ANCOVA models were applied to compare 12-weeks periods of treatment. RESULTS: One-thousand-three-hundred-fifty-one PGB-naive patients [55.8% women, 56.7 (12.5) years] were analyzed: 490 (36%) switched to PGB as monotherapy (PGBm), 702 (52%) patients received PGB as add-on therapy (PGBadd-on), and in 159 (12%) previous treatment was replaced by a regimen not including PGB (Non-PGB). As compared to non-PGB, both PGBm and PGBadd-on showed significantly higher HRU reduction. The extra costs of drugs, particularly in PGB subgroups [€15.4 (39.1), €148.6 (109.1) and €145.3 (119.6), respectively (p<0.0001 within and between groups)] was off-set by higher significant reductions in all other components of health costs (except non-pharmacological therapies in non-PGB group) yielding to a greater total cost reductions: €1203.3 (1805.6), €1423.2 (1650.0) and €1429.2 (1966.2), respectively (p<0.001 within and p=0.0004 between groups). CONCLUSION: In the primary care setting either add-on or monotherapy with pregabalin under routine medical practice was associated with a significant longitudinal reduction in HRU and total costs when compared with non-PGB therapy in subjects with painful radiculopathy of cervical or lumbar origin.