This study evaluates whether the cardiac autonomic response to head-up tilt test (HUTT) differs between patients with relapsing-remitting multiple sclerosis (RRMS) and those with progressive MS (PMS) as compared to healthy controls (HC). Baroreflex sensitivity, cardiac parameters, heart rate (HRV) and blood pressure variability (BPV) were compared between 28 RRMS, 21PMS and 25 HC during HUTT. At rest, PMS patients had higher values of the sympathovagal ratio, a low-frequency band HRV (LFnu-RRI) and lower values of parasympathetic parameters (HFnu-RRI, HF-RRI) compared to RRMS and HC. Resting values of cardiac parameters were significantly lower in RRMS compared to PMS patients. No intergroup differences were observed for post-tilt cardiac and autonomic parameters, except for delta HF-RRI with lower values in the PMS group. The MS variant corrected for age, sex and Expanded Disability Status Scale (EDSS) score was an independent predictor of changes in the sympathovagal ratio as measured by HRV. Furthermore, a higher overall EDDS score was related to a higher sympathovagal ratio, lower parasympathetic parameters at rest, and decrease post-tilt changes of the sympathovagal ratio of sBP BPV. Autonomic imbalance is markedly altered in the MS patient group compared to control changes were most pronounced in the progressive variant of MS disease. The MS variant appeared to have a potential influence on cardiac autonomic imbalance at rest.