Objective: Previous experiments have demonstrated that several inflammatory biomarkers, including pentraxin 3 (PTX3), matrix metalloprotein 9 (MMP9), interleukin-6 (IL-6), and the neutrophil to lymphocyte ratio (NLR), are differentially elevated in coronary artery disease (CAD). This study aims to compare the associations between plasma levels of these biomarkers and CAD, identifying the best biomarker that has the most powerful association with CAD. Methods: Blood samples were collected from 64 patients admitted to the Department of Cardiology, 31 of whom had CAD and 33 of whom were CAD-free. Plasma levels of PTX3, MMP9, and IL-6 were measured via ELISA. The coronary Gensini score was used to evaluate the severity of coronary artery lesions. Results: PTX3 levels and NLR levels between the CAD group and the CAD-free group were statistically significant (P < 0.05). Stepwise multiple linear regression analysis showed that PTX3 levels and NLR levels were independently associated with CAD (r = 1.3, P < 0.05; r = 1.8, P < 0.05). Only PTX3 was associated with the severity of coronary artery stenosis. A PTX3 threshold of 4.38 ng/mL maximized true-positive and false-negative results. PTX3 displayed a greater area under the receiver operating characteristic curve (AUC) than NLR, MMP9, and IL-6 (0.733 versus 0.612 versus 0.725 versus 0.518). Conclusions: Compared to NLR, MMP9, and IL-6, PTX3 displayed greater AUC and association with CAD. PTX3 may become a potentially powerful inflammatory biomarker for CAD.