Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates pro-inflammatory molecules from oxidized LDL. We examined the association between Lp-PLA2 plasma concentrations and risk of stable coronary artery disease (CAD) in a large case-control study and further assessed the relationship between Lp-PLA2 and various lipid, inflammatory and hemostatic parameters. Lp-PLA2 concentrations were measured in 312 patients with CAD and in 479 age- and gender-matched blood donors. Various sensitive inflammatory and hemostatic markers and a complete lipoprotein profile were obtained. Lp-PLA2 concentrations were significantly higher in cases than in controls (296.1 ng/mL versus 266.0 ng/mL, p<0.0001). In multivariable logistic regression, the age- and gender-adjusted OR for the presence of CAD was 1.61 (95% CI, 1.07-2.44) if the top quartile of the Lp-PLA2 distribution was compared to the bottom quartile. Adjustment for traditional cardiovascular risk factors and statin use resulted in an OR of 2.04 (95% CI, 1.19-3.48). After additional controlling for vWF, the OR was slightly attenuated but still remained statistically significant (OR 1.91; 95% CI, 1.12-3.28). Thus, elevated Lp-PLA2 concentrations were associated with the presence of stable CAD, independent of various biochemical markers. Our results support the hypothesis that Lp-PLA2 may be a novel, independent risk marker for CAD.