ABSTRACT: To examine the long-term effects of type 1 diabetes treatment, metabolic control, and complications on health-related quality of life (HRQOL).A total of 1,441 participants, initially 13-39 years of age, were followed for an average of 23.5 years as part of the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study. The Diabetes Quality-of-Life questionnaire (DQOL) was administered annually during DCCT and every other year during EDIC. Biomedical data, including HbA1c levels, exposure to severe hypoglycemia, intercurrent psychiatric events, and development of diabetes complications were collected at regular intervals throughout the follow-up.Mean total DQOL scores were not significantly different between the former DCCT intensive and conventional treatment groups (DCCT baseline, 78±8 vs. 78±9; EDIC year 17, 75±11 vs. 74±11). Over the course of the study, a drop of ?5 points in DQOL score from DCCT baseline maintained on two successive visits occurred in 755 individuals and was associated with increased HbA1c, albumin excretion rate, mean blood pressure, BMI, and occurrence of hypoglycemic events requiring assistance. Lower DQOL scores after 23.5 years of follow-up were associated with prior development of retinopathy (P=0.0196), nephropathy (P=0.0019), and neuropathy (P<0.0001) as well as self-reported chest pain (P=0.0004), decreased vision in both eyes (P=0.0005), painful paresthesias (P<0.0001), recurrent urinary incontinence (P=0.0001), erectile dysfunction (P<0.0001), and history of psychiatric events (P<0.0001).Among DCCT/EDIC participants, worsening metabolic control, serious diabetes complications and their associated symptoms, and development of psychiatric conditions led to decreased HRQOL.