Aims To assess the child- and parent-reported health-related quality of life (HRQOL) of children with joint hypermobility syndrome (JHS), to compare these with other chronic paediatric conditions and to determine whether symptoms experienced by children with JHS can predict their HRQOL. Methods Eighty-nine children with JHS and one of their parents completed the Pediatric Quality of Life Inventory 4.0 Generic Core Scale, the Multidimensional Fatigue Scale and the Pediatric Pain Questionnaire. Anthropometric measures and reported symptoms were recorded. Child-reported HRQOL scores were compared with parent report, and both child- and parent-reported HRQOL scores of children with JHS were compared with those of children with other chronic conditions. Stepwise multiple regression was undertaken to determine whether any combination of measures could predict HRQOL. Results Parent- and child-reported HRQOL scores were strongly correlated (r = 0.6-0.84, all P < 0.001); however, parents of children with JHS perceived lower overall HRQOL (mean difference = 4.44, P = 0.001), physical (mean difference = 7.11, P < 0.0001) and emotional functioning (mean difference = 5.24, P = 0.011) than their children. When considered together with previously reported HRQOL scores for children with other chronic conditions, parent and child scores were similarly strongly correlated (r = 0.93, P = 0.001). Multiple regression revealed that 75% of the variance in child-reported HRQOL scores was accounted for by a child's level of pain and fatigue, and presence of stress incontinence symptoms (P < 0.0001). Conclusion Children with JHS experience poor HRQOL and disabling fatigue, with parent scores providing a good proxy. Pain, fatigue and the presence of stress incontinence symptoms have the greatest impact on their HRQOL.