OBJECTIVETo establish minimal clinically important difference (MCID) scores representing the smallest detectable change in quality of life (QOL), using the Pediatric Quality of Life Inventory (PedsQL) Generic Core and Diabetes Module among youth with diabetes and their parents, and to identify demographic and clinical correlates of QOL change over 1 year.RESEARCH DESIGN AND METHODSParticipants in the SEARCH for Diabetes in Youth Study aged >5 years and parents of youth aged <18 years completed PedsQL surveys at their initial and 12-month study visits. MCIDs for each PedsQL module were calculated using one standard error of measurement. Demographic and clinical characteristics associated with QOL change were identified through multiple linear and logistic regression analyses.RESULTSThe sample comprised 5,004 youth (mean age, 12.5 ± 4.7 years; mean diabetes duration, 3.4 ± 3.7 years). Of 100 possible points, PedsQL total score MCIDs for youth with type 1 and type 2 diabetes, respectively, were Generic Core, 4.88, 6.27 (parent) and 4.72, 5.41 (youth); Diabetes Module, 4.54, 6.06 (parent) and 5.27, 5.96 (youth). Among 1,402 youth with a follow-up visit, lower baseline QOL, male sex, private insurance, having type 1 diabetes, longer diabetes duration, and better glycemic control predicted improvements in youth- and parent-reported PedsQL total scores over 1 year. Clinically meaningful (≥1 MCID) improvements in total score for at least one PedsQL module were predicted by private insurance, lower BMI, and lower A1C at baseline.CONCLUSIONSThese diabetes-specific reference points to interpret clinically meaningful change in PedsQL scores can be used in clinical care and research for youth with type 1 and type 2 diabetes.