Postural tachycardia syndrome (POTS) is a fairly common condition that may or may not be associated with autonomic neuropathy. In a retrospective analysis, we compared two groups of patients based on clinical and autonomic criteria, those with POTS in isolation (POTS-Alone), and POTS with evidence of autonomic neuropathy (POTS-AN). Of 260 records reviewed, 57 patients met the criteria for POTS; 38 (67%) patients assigned to the POTS-Alone group and 19 (33%) patients assigned to the POTS-AN group. A decreased sweat output on the quantitative sudomotor axon reflex test is the most frequent abnormal finding in the POST-AN group suggesting sympathetic cholinergic neuropathy. Clinically, headache and gastrointestinal symptoms were more frequent among the POTS-AN group. Therefore, POTS may exist in isolation and may differ from those associated with AN.