Health-Related Quality of Life (HRQoL) assessments in spinal disease offer the potential of outcome measures that better represent patients' disability and response to treatment. The Short Form 36 Health Survey (SF-36) is a generic HRQoL questionnaire that has been extensively used in primary and secondary care, but before it can be routinely applied in patients with spinal disease must be validated against traditional specific measures of physical and mental morbidity. Patients with lumbar disc prolapse, lumbar canal stenosis, and cervical spondylotic radiculomyelopathy were identified from a prospectively maintained database. Visual Analogue Scales (VAS) and condition-specific questionnaires including the Roland Morris Disability Score (RMDS), Myelopathy Disability Index (MDI), and Hospital Anxiety and Depression Scales (HADS), were completed alongside the SF-36 survey at baseline and following surgery. Convergent, discriminant, and predictive validity were assessed by computing correlations between the specific and generic scores. In addition, responsiveness (Standardised Response Mean, SRM) and floor and ceiling effects were examined. Data from 1623 assessments of 620 patients were available. Convergent validity was shown by strong correlations between condition-specific physical scores (MDI or RMDS) and the Physical Function and Bodily Pain domains of SF-36 (ρ = -0.52 to -0.76, all p < 0.01). VAS for leg or arm pain were also strongly correlated with Bodily Pain domain scores (ρ = -0.54 to -0.77, all p < 0.01). Discriminant validity was confirmed by non-significant partial correlations between Physical Function and Mental Health SF-36 domains when controlled for HADS scores (r = −0.01 to 0.02, p > 0.05). Predictive validity was demonstrated by similar correlations between pre- and post-operative scores for specific and generic instruments. Physical Function, Bodily Pain, and Mental Health domains were all free of significant floor or ceiling effects and showed moderate to good responsiveness (SRM 0.54-1.72). SF-36 domain scores are valid for measuring morbidity and surgical outcomes in common spinal disorders.