A retrospective review identified 99 adolescents (79% female) referred to a tertiary care center to evaluate the relationship between symptoms of orthostatic intolerance and chronic pain. Regression analysis indicated that functional disability was strongly associated with pain intensity (P < .001) and depression (P = .024). The association between functional disability and number of symptoms of orthostatic intolerance trended toward significance (P = .057). Meeting a threshold heart rate increment of 30 beats per minute on head-up tilt was not associated with functional disability (P = .188). Separate regression analysis of female patients showed similar results to the full sample but with a stronger relationship between depression and functional disability and a weaker relationship between heart increment and functional disability. In this sample of adolescents with symptoms of orthostatic intolerance and chronic pain, pain intensity and depression were associated with functional status, but postural tachycardia was not. Further research is needed to clarify potential gender differences.