BackgroundOrthostatic intolerance (OI), which is common in children and adolescents, negatively impacts their quality of life (QOL) due to physical symptoms that limit work, school, and daily activities. The purpose of this study is to explore the association of physical and psychosocial factors with QOL scores in children and adolescents with OI.MethodsA cross sectional observational study was conducted. The study participants included 95 Japanese pediatric patients of age 9–15 years who were diagnosed with OI from April 2010 to March 2020. The QOL scores and the QOL T-scores of children with OI assessed using the KINDL-R questionnaire at the initial visit were compared with conventional normative data. The associations of physical and psychosocial factors with the QOL T-scores were examined using multiple linear regression.ResultsPediatric patients with OI had significantly lower QOL scores than healthy children in both elementary (50.7 ± 13.5 vs. 67.9 ± 13.4,p< 0.001) and junior high schools (51.8 ± 14.6 vs. 61.3 ± 12.6,p< 0.001). This finding was observed in the physical, mental, self-esteem, friends, and school domains. Total QOL scores were significantly associated with school nonattendance (β =  − 3.2, 95% confidence interval [CI] =  − 5.8 to − 0.5,p= 0.022) and poor relationship with school (β =  − 5.0, 95% CI =  − 9.8 to − 0.4,p= 0.035).ConclusionsThese results suggest that the assessment of QOL, including both physical and psychosocial aspects, especially school factors, needs to be implemented earlier in children and adolescents with OI.