This cross-sectional study tested the hypothesis that decreased serum levels of tetranectin (TN), a regulator of the fibrinolysis and proteolytic system, is associated with the presence and severity of CAD. We conducted a systematic serological and immunohistochemical (IHC) analysis to respectively compare the TN levels in serum and artery samples in CAD patients and healthy controls. Our results showed that serum levels of TN were significantly lower in patients with CAD than in healthy controls. Further analysis via trend tests revealed that serum TN levels correlated with the number of diseased arteries. Besides, the multivariate logistic regression model revealed TN as an independent factor associated with the presence of CAD. Additionally, IHC analysis showed that TN expression was significantly higher in atherosclerotic arteries as compared to healthy control tissues. In conclusion, our study suggests that increased serum TN level is associated with the presence and severity of diseased coronary arteries in patients with stable CAD.