BACKGROUND Severity of stenosis remains the main factor for assessing risk of stroke in patients with internal carotid artery (ICA) disease. This study was conducted to investigate the association of plaque echostructure and other established and emerging cardiovascular risk factors with symptomatic ICA disease. METHODS Cross-sectional study of consecutive patients with significant (> 50%) ICA stenosis. METHODS Carotid plaque echostructure, smoking, hypertension, diabetes mellitus, serum lipoprotein (a), homocysteine, vitamin B12, folate, cholesterol to high-density lipoprotein ratio, triglycerides, C-reactive protein, and the Framingham risk score were assessed in 124 consecutive patients (70 asymptomatic; 54 symptomatic) with significant (> 50%) ICA stenosis. RESULTS The asymptomatic and symptomatic groups did not differ in terms of gender distribution (p = 0.76) and severity of stenosis (p = 0.62). Echolucent plaques (type 1 and 2) were more predominant in patients with symptomatic disease (p = 0.004, OR = 2.13, 95% CI = 1.26-3.6). Patients with plaques type 1 were relatively younger than those with type 4 (p = 0.02). None of the other factors assessed had any significant association with symptomatic disease and any type of carotid plaque. CONCLUSIONS Besides the severity of carotid stenosis, the presence of an echolucent plaque appears as an important factor associated with symptomatic ICA disease. Also, young patients are more likely to have an echolucent plaque suggesting an age-related association with plaque maturation.