PURPOSE: Health-related quality of life (HRQoL) is an important patient-reported outcome in clinical and health research. The EQ-5D-Y assesses child and adolescent HRQoL by five items on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as a visual analogue scale (VAS) on the current health state. This study investigates predictors of self-reported HRQoL according to the EQ-5D-Y in chronically ill children and adolescents using longitudinal data. METHODS: Data from the German Kids-CAT study on children and adolescents with asthma, diabetes, and juvenile arthritis gathered over a period of six months were analyzed (n = 310; 7-17 years old; 48% female). Self-, parent-, and pediatrician-reported data were collected from June 2013 to October 2014. Generalized linear mixed models and linear mixed models served to examine effects of socio-demographic as well as disease- and health-specific predictors on the items as well as on the VAS of the EQ-5D-Y. RESULTS: Ceiling effects for the EQ-5D-Y indicated low burden of disease in the analyzed sample. Longitudinal analyses revealed associations between less health complaints and better HRQoL for all investigated HRQoL domains. Further, age- and gender-specific effects, and associations of better disease control, longer duration of the disease and less mental health problems with better HRQoL were found. CONCLUSIONS: Subjective health complaints and mental health problems should be considered in the care of children and adolescents with asthma, diabetes, and juvenile arthritis. Future research should suggest administering the items of the EQ-5D-Y with five instead of three response options, and investigate HRQoL over a longer period.