Venous echo-color-Doppler (ECD) showed that chronic cerebrospinal venous insufficiency (CCSVI) syndrome is related to multiple sclerosis (MS). Study aims were to assess interobserver variability in ultrasound evaluation of MS patients and to relate echo-markers to MS clinical symptoms and the disability degree. 277 MS patients (117 men, mean age 43.05+10.04 years) admitted to the Neurology Department of Bari University General Hospital, underwent clinical, Expanded Disability Status Scale (EDSS) evaluation, and a cerebro-venous system ECD evaluation. Two operators reevaluated 32 patients to calculate interobserver variability. McNemar test confirmed the procedure reproducibility between two operators (p=ns). Septa/membranes correlated with deep cerebral veins reflux [right: 16% absence vs. 58% presence, p < 0.0001; left: 26% vs. 50%, p < 0.0001]; their absence in Primary Progressive (PP) MS form [right: 11% vs. 2%, p < 0.001; left: 12% vs. 2%, p < 0.001]. Internal jugular veins (IJVs) reflux absence was in Relapsing-remitting (RR) form [right: 60% vs. 74%, p=0.036; left: 56% vs. 85%, p < 0.0001] like hemodynamically significant stenosis [right: 57% vs. 69%, p=0.033; left: 49% vs. 73%, p < 0.001] not present in PP [right: 11% vs. 2%, p < 0.001; left: 10% vs. 3%, p=0.009]. A supine IJVs blocked flow was related to the EDSS class [right: 4.8±1.5 vs. 5.4±1.4, p=0.006; left: 4.7±1.6 vs. 5.5±1.2, p < 0.0001]; its absence was linked to RR [right: 60% vs. 76%, p=0.016; left: 58% vs. 79%, p < 0.001]. ECD has an important value in MS patients with IJV anomalies detection and a good interobserver procedure reproducibility. MS is associated with CCSVI, although further studies are needed.