OBJECTIVES: The goal of this cross-sectional analysis was to determine pain impact on Quality of Life (QoL) and interference with disability among patients with chronic NeP. METHODS: Participants in an observational, prospective and multicentre study in Spain (DONEGA study) with NeP of different etiologies, completed the Short Form-McGill Pain Questionnaire (SF-MPQ), the MOS Short Form-12 (SF-12), and the Sheehan Disability Scale at baseline. RESULTS: A total of 1519 patients [mean ± SD; 56.0±13.7 years old (58.8% female)] with NeP were enrolled in the study. Patients had NeP for 1.1±2.8 years, and 83.3% were on any type of analgesic treatment at baseline: oral analgesics (51.2%), topical analgesics (26.9%), NSAID's (11.1%), antiepileptics (7.3%), and psychoanaleptics (3.5%). Average Pain scores were 13.1±8.2 pts., 10.0±5.8 pts., and 3.1±3.3 pts., for total scale (range 0–45), sensory domain (range 0-33), and affective domain (range 0-12), respectively. Present pain intensity was 2.8±1.0 (range 0-5) and mean pain past week on a VAS scale was 71.2±18.9 mm. Pain substantially interfered (≥5 on 0 – 10 scale) with normal work (6.0±3.1), social life (5.7±3.0), and family life (5.3±3.0), then producing disability; Sheehan total (on 0–30 scale): 17.0±8.4 pts. Country normalized physical (PCS) and mental health (MCS) component summary scores (SF-12) indicated significant impairment in both domains compared to the general Spanish population: PCS; 37.6±6.0 vs. 50.1±9.5, and MCS; 45.9±8.1 vs. 50.0±9.6, respectively. Increasing levels of refractory pain, as assessed by number of medications, corresponded to increasing levels of disability (Sheehan total: 14.2±8.8 to 16.4±8.3, to 18.7±8.1, and to 20.6±7.0, by 0, 1, 2, and 3 medications respectively, p<0.01 for all between group comparisons except 2 vs. 3). CONCLUSIONS: NeP decreases patients’ physical and mental components of QoL, while increasing level of disability and impaired normal work. The disability increases with level of pain treatment resistance.