We assessed the impact of health problems in children and young adults with spina bifida on their health-related quality of life. Design: We surveyed 124 children and young adults with spina bifida in central florida identified through multiple sources including multi-specialty clinic rosters, Title V clinic registries, and community-based spina bifida associations. The Child Health Questionnaire, CHQ) and SF-36 were used to assess health related quality of life (HRQOL). Results: the sample included 84 children age 5 to 17 years old and 40 young adults age 18 to 30 years old. In the past year, more than half (55%) had experienced a bladder infection, 40% pressure sores, 39% an allergy to latex, 385 scoliosis or kyphosis, 32% chronic pain, and 37% a weight problem. Children with chronic pain (versus those without chronic pain) reported the largest difference in HRQOL scores in both the psychosocial or physical health areas: physical HRQOL; 24.7 vs. 37.5, p < .01; psychosocial HRQOL; 48.7 vs. 41.4, p < .01. Adults with chronic pain reported significantly lower pyschosocial health scores (46.0 vs. 58.1, p < .01. Other conditions associated with significantly reduced HRQOL scores were pressure sores and bladder infections in children and latex allergy in adults. Conclusions: In both children and adults with spina bifida, chronic pain has a substantial negative impact on physical and psychosocial health-related quality of life. In order to maximize the quality of life of persons with spina bifida, increased efforts are warranted to identify and control chronic pain.