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Postural tachycardia syndrome (PoTS) is a poorly understood disorder characterized by excessive tachycardia in the upright position. In addition, patients with PoTS often complain of non-postural symptoms, including fatigue, gastrointestinal and vasomotor fluctuations. The present study quantitatively assessed autonomic symptom burden in PoTS patients (n = 32) using the COMPASS-31, compared to that of autonomic failure/neuropathy (AF/N; n = 47) and asymptomatic, healthy controls (n = 32). Using AIC model selection and regression analysis, we found differences in the contribution of individual COMPASS-31 domains, depending on the autonomic disorder. In PoTS, fatigue severity, orthostatic intolerance and pupillomotor symptom domains, contributed significantly to differences in COMPASS-31 scores compared to controls. In contrast, the secretomotor, gastrointestinal, bladder and vasomotor domains, contributed significantly to the AF/N model. Our results confirm an increase in autonomic symptoms across all functional domains in PoTS compared to controls, and with similar severity to AF/N, though with differing significant domain contributions. Our findings provide additional support that PoTS is indeed a syndrome of autonomic dysfunction beyond orthostatic intolerance, but also indicates the likelihood of disease-specific contributions to symptom burden, highlighting the need for application of expanded physiological assessment beyond orthostatic challenge, as well as disease-specific symptom assessment tools for use in PoTS. [ABSTRACT FROM AUTHOR]