Neuropathic pain is frequently associated with negative effects on quality of life (QoL), affecting physical, social, and psychological functioning. Of many existing scales used to measure QoL, none have been validated in a neuropathic pain patient population. This study reports on the development and preliminary psychometric evaluation of the Neuropathic Pain Impact on Quality-of-Life questionnaire (NePIQoL), a measure to assess QoL in neuropathic pain. In Phase I, focus groups with 27 patients and a panel of experts identified QoL issues for inclusion in the measure. Initial items (152) and response categories were pretested using cognitive interviewing (18 patients). Following this, the number of items was reduced to 91. In Phase II, the 91-item version of the NePIQoL was administered to a further 112 patients, poorly performing items were identified, and internal consistency was examined. In Phase III, the revised NePIQoL was administered to a further 110 patients on two occasions to examine validity and test-retest reliability. Qualitative and quantitative pretesting led to extensive revision, resulting in a final measure of 42 items. Finally, Phase IV tested the concurrent validity and responsiveness of the NePIQoL. The authors conclude that the NePIQoL is an acceptable, patient-derived, neuropathic pain-specific measure with evidence of reliability, validity, and temporal stability.