The purpose of this study was to identify factors associated with health-related quality of life (HRQOL) in individuals with myelomeningocele. Eighteen female and 16 male patients with myelomeningocele (mean age 13y, SD 6y; range 4 to 27y) were prospectively enrolled. Twenty-four of the patients had lesions at or above the L4 level, and 11 were wheelchair dependent. Twenty-five patients had shunted hydrocephalus; mean IQ of the cohort on testing was 85 (SD 18; range 36 to 111). Functional independence was measured in three areas (self-care, mobility, and social cognition) using the Functional Independence Measure for Children (WeeFIM). The Support Function Scale (social supports available to the family), the Amount of Assistance Questionnaire (assistance required for activities of daily living), and the Health Utilities Index II (HUI-II; perceived health status measure) were completed by participants or their parents. Each patient's HRQOL was quantified using a ‘feeling thermometer’, which is a plastic ‘thermometer’ scaled from 0 (least desirable health state) to 100 (perfect health). Results of multiple regression analysis using HRQOL as the dependent variable revealed that the Amount of Assistance Questionnaire, WeeFIM self-care, and HUI-II were significantly correlated with quality of life ratings (p<0.025). Maximizing functional independence should be a priority in improving HRQOL in individuals with myelomeningocele.