Brain-derived neurotrophic factor (BDNF) plays a functional role in vascular endothelium homeostasis and the alleviation of atherosclerosis. Matrix gla protein (MGP) and Nε-(1-carboxymethyl)-l-lysine (CML) are both confirmed to be VC predictors. This study investigated the association between BDNF, MGP, CML and coronary artery calcification (CAC). Plasma BDNF, MGP, and CML levels were measured in 274 patients who underwent computed tomography to determine the CAC score (Agatston score). It was found that patients with CAC exhibited lower BDNF and MGP and higher CML levels than those without CAC. Plasma BDNF levels in patients with diabetes or hypertension were lower compared with the control groups. In logistic regression analysis, age, hypertension, BDNF, and MGP were independent predictors of CAC. Plasma BDNF and MGP levels were both correlated with the Agatston score even after adjustment for age, total cholesterol level, triglycerides, low-density lipoprotein level, creatinine clearance rate, and the presence of hypertension and diabetes mellitus. In 167 patients with CAC, circulating BDNF level was inversely associated with CML level and positively related to MGP level. In the receiver operating characteristic analysis for CAC, the areas under the curves for BDNF, MGP, and CML were 0.757, 0.777 and 0.653, respectively. In summary, plasma BDNF levels are associated with the Agatston score, and BDNF further predicts the occurrence of CAC.