PURPOSE: To validate a glaucoma-specific health-related quality of life (HRQoL) questionnaire: the Glau-QoL. METHODS: Patients with ocular hypertension (OHT) or glaucoma took part in a cross-sectional psychometric validation study (n = 573) and a separate reproducibility study (n = 244). Patients answered the 36-item Glau-QoL, designed from in-depth patient interviews. RESULTS: The clinical validity of the Glau-QoL was excellent and clearly demonstrated that as disease severity and visual field impairment increased, HRQoL scores for the Psychological Wellbeing, Self-image, Daily Life, Driving, Anxiety and Burden of Treatment domains were negatively affected. Increased age and lower visual acuity were also associated with lower HRQoL scores, although to a lesser extent than the previously mentioned criteria. Worsening of HRQoL domains correlated with the clinical stage of glaucoma: Anxiety and Burden of Treatment scores dropped noticeably when patients were first diagnosed and started treatment, followed by a decrease in scores for Driving, Daily Life, Psychological Wellbeing, and Self-image as clinical conditions worsened. Psychometric validation showed acceptable convergent and discriminant validity of the Glau-QoL, and good reproducibility, with intraclass correlation coefficients (ICC) and concordance correlation coefficients (CCC) > or = 0.69. Internal consistency reliability was high (Cronbach's alpha coefficients > 0.70) for the Daily Life, Psychological Wellbeing, Burden of Treatment and Driving domains; acceptable (coefficients of 0.65 and 0.68, respectively) for the Self-image and Anxiety domains; and weak (coefficient = 0.58) for the Confidence in Health Care domain. CONCLUSIONS: The Glau-QoL questionnaire is a valid and specific HRQoL instrument that demonstrates excellent correlations with disease progression in patients with glaucoma and/or OHT.