BACKGROUND: The aim of this study was to investigate the relationship of autonomic dysfunction and clinical findings in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: For the assessment of autonomic dysfunction, heart rate variability (HRV) and blood pressure (BP) measurement to deep breathing, Valsalva maneuver or head tilt-table test, with quantitative sudomotor axon reflex test (QSART) were used and interpreted in the form of the composite autonomic scoring scale (CASS). Clinical and radiological correlates with autonomic profiles were analyzed. RESULTS: A total of 27 patients (mean age, 44.4 +/- 12.26 years; female: male=22:5) were enrolled in this study and 74.1% of them showed autonomic dysfunction, involving the adrenergic, cardiovagal, or sudomotor domains. Eighteen patients were during remission, in whom, demographics and MRI findings were associated with an index or a total score of CASS. The presence of cervical cord lesion showed the association with cardiovagal index (B = 0.750, S.E. 0.242, 95% CI 0.237-1.263, p = 0.007), male gender with sudomotor index (B = 1.600, S.E. 0.653, 95% CI 0.199-3.001, p = 0.028) and the involvement of brain and/or spinal cord with a total CASS score (B = 1.500, S.E. 0.655, 95% CI 0.096-2.904, p = 0.038). In multivariable analysis, delayed pressure recovery time showed a significant positive association with EDSS score (B = 0.103, S.E. 0.031, 95% CI 0.037-0.168, p = 0.004). DISCUSSION: Cardiovascular and sudomotor autonomic dysfunction are common in NMOSD. Several clinical and MRI characteristics of patients may warrant the investigation of autonomic dysfunction and its proper management.