OBJECTIVES Most of the extra-cranial venous abnormalities have been previously described as truncular venous malformations. In this hypothesis-driven study, we evaluated possible association of risk/protective factors with the presence of truncular and functional venous abnormalities in internal jugular veins (IJVs) in a large cohort of volunteers without known central nervous system (CNS) pathology. METHODS The study included 240 controls who underwent physical and Doppler sonography (DS) examinations for the presence of intra- and extra-luminal structural and functional abnormalities of the IJVs, and were assessed with a physical examination and structured environmental questionnaire for demographic characteristics, presence of autoimmune and other concomitant diseases, vascular risk factors, environmental factors, and habits. Logistic regression analysis was used to test which risk/protective factors were associated with the presence and number of extra-cranial venous abnormalities. RESULTS Subjects with heart disease (P<0·001), overweight (P = 0·005), and smoking (P = 0·016) had a significantly increased number of intra-luminal structural venous abnormalities. Presence of heart disease increased the risk of a malformed valve 12·9 times (95% CI: 5·4-31·3, P<0·001), while smoking increased it 2·21 times (95% CI: 1-4·9, P = 0·033). Being overweight (P = 0·003), a history of mononucleosis (P = 0·012) and smoking (P = 0·042) increased risk for presence of a flap. No association was found between the investigated risk factors and extra-luminal or functional venous abnormalities. However, use of dietary and herbal supplements had a protective role for the presence of functional venous abnormalities. CONCLUSIONS There is a close association between intra-luminal, structural, extra-cranial, venous system pathology and the presence of heart disease, overweight, and smoking.