This study was designed to examine the distribution of plasma soluble CD40 ligand (sCD40L), and its relationship with carotid intima-media thickness (CIMT) in healthy controls and subjects with white-coat hypertension (WCH) or hypertension (HT). Thirty-five patients with HT, 35 patients with WCH, and 35 healthy controls were enrolled. The normal group (CIMT < 0.9 mm), subclinical atherosclerosis group (0.9 mm ≤ CIMT < 1.2 mm) and atherosclerosis group (CIMT ≥ 1.2 mm) were grouped based on the value of CIMT. The highest level of sCD40L was observed in HT group, followed by WCH group and healthy controls. The level of sCD40L was significantly increased in atherosclerosis group compared with subclinical atherosclerosis group and healthy controls. In the WCH group, sCD40L level was significantly and positively correlated with CIMT and systolic blood pressure. Multiple logistic regression indicated that sCD40L was a risk factor for increased CIMT (odds ratio, 1.504; 95% confidence interval, 1.054-1.956, P < 0.001). The data provided evidence that sCD40L levels in subjects with WCH and HT were significantly and consistently higher than those in healthy controls. SCD40L may represent a potential non-invasive atherosclerosis marker in WCH patients.