OBJECTIVES:To analyze all the arguments against chronic cerebrospinal venous insufficiency (CCSVI) as a medical entity, and its association with multiple sclerosis (MS) and to revise all the findings suggesting a possible connection between these two entities. METHODS:We revised the methodology and results of all fourteen published studies on prevalence of CCSVI in MS patients. Furthermore, we take into consideration other work dealing with possible causes and explanations of venous, as well as vascular dysfunctions linked with MS. RESULTS:Studies of prevalence show a great variability in prevalence of CCSVI in MS patients. However, a recent meta-analysis assessed an over 13 times increased prevalence in MS. Global hypoperfusion of the brain, and reduced cerebral spinal fluid dynamics in MS was shown to be related to CCSVI. Post-mortem studies show a higher prevalence of intraluminal defects in the main extracranial vein in MS patients in respect to controls. DISCUSSION:Taking into account the current epidemiological data, the autoptic findings, and the relationship between CCSVI and both hypoperfusion and cerebrospinal fluid flow, CCSVI can be inserted in the list of multiple factors involved in MS pathogenesis. Our careful data analysis may conclude that great variability in prevalence of CCSVI in MS patients can be a result of different methodologies used in venous ultrasound assessment. Finally, it has been proven that CCSVI share the three main risk factors with MS. On the other hand, smoking is the most important risk factor for endothelial cell damage, vitamin D has a protective role and Epstein-Barr virus passes the blood-brain barrier by invading the endothelial cells, therefore, epidemiologically, linking the imbalance of these three factors to MS through autoimmunity.