The aim of the study was to investigate self-reported health-related quality of life (HRQOL) in children and adolescents with myelomeningocele (MMC) and to examine the impact of clinical impairments and limitations in activities of daily living (ADL). Fifty patients (28 females, 22 males) between 8 and 16 years of age (mean age 12y 1mo [SD 2y 4mo]) with MMC from three German paediatric centres and their mothers completed standardized measures on HRQOL (KINDL-R) and limitations in ADL (Childhood Health Assessment Questionnaire). Lesion level was thoracic in nine, sacral in 25, and lumbosacral in 11 patients. Twenty-one patients were community walkers, 17 were able to walk in the home, and seven used a wheelchair. Two-thirds had health problems related to the central nervous system causing current difficulties (eight patients had a shunt, six had hydrocephalus, and 10 had a tethered cord). Patients in the study group reported diminished overall HRQOL compared with norm data, specifically in the dimensions of emotional well-being, self-esteem, and peer relations. Adolescents reported diminished HRQOL in the dimension of peer relations. Most medical parameters as well as limitations in ADL were not significantly associated with HRQOL. Our findings confirm the results of studies which dispute a linear inverse association between condition severity and HRQOL and emphasize the importance of peer relations in young patients with MMC.