Objectives: To examine the association of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) overall and specific scale scores with visual acuity, diabetic retinopathy, and other characteristics, in a cohort of persons with type 1 diabetes. Design: Population-based cohort study. Setting: An 11-county area in southern Wisconsin. Participants: Six hundred two persons with diabetes whose conditions were diagnosed when they Were younger than 30 years and who were currently taking insulin participated in baseline, 4-year, 10-year, and 14-year follow-up examinations. Main Outcome Measures: An interview that consisted of the 25-item NEI-VFQ was completed, visual acuity was measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol and the presence and severity of retinopathy and macular edema were detected by masked grading of stereoscopic color fundus photographs using the modified Airlie House classification and the ETDRS retinopathy severity scheme. Results: Univariate analyses revealed that the total NEI-VFQ-25 score was lower in persons who were older, had a longer duration of diabetes, higher glycosylated hemoglobin, were in renal failure, had a history of cardiovascular disease, hypertension, or amputation of a lower limb, had poorer visual acuity, more severe diabetic retinopathy, macular edema, glaucoma, cataract, abnormalities in tactile sensation or temperature sensitivity, smoked more total pack-years, led a more sedentary lifestyle, and had poor peak expiratory flow. In multivariate analyses, while controlling for the physical and mental component scores from the Medical Outcomes Survey 36-Item Short-Form Health Survey as measures of comorbidity, lower total NEI-VFQ-25 scores were independently associated with poorer visual acuity, more severe retinopathy, older age, history of loss of tactile sensation, and more total pack-years of cigarettes smoked. Conclusions: In this cross-sectional study, the 25-item NEI-VFQ seems to be strongly associated with vision, independent of severity of retinopathy and other complications associated with type 1 diabetes. It may be a useful measure of health-related quality of life as it relates to vision in epidemiological studies and clinical trials in persons with diabetes.