Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) has recently been shown to be positively related to coronary events in patients with coronary artery disease (CAD). However, direct evidence about the relationship between circulation Lp-PLA2 activity and vulnerable plaque in patients with CAD remains lacking.Methods Plasma Lp-PLA2 activity was determined in 146 consecutive patients with CAD who underwent clinically-indicated coronary angiography and preinterventional intravascuiar ultrasound (IVUS).Results Eighty-three patients were included in the final analysis after the initial screening. Sixty (72.3%) were acute coronary syndrome (ACS) patients and 23 (27.7%) were stable angina pectoris (SAP) patients. Plaque rupture occurred in 39 (47.0%) patients, and 34 (87.2%) were from ACS patients and 5 (12.8%) from SAP patients. There were no significant differences in clinical and angiographic characteristics between patients with plaque rupture and those without plaque rupture, except for smoking, high-sensitive C-reactive protein (hs-CRP) level and Lp-PLA2 activity (all P ＜0.05).IVUS measurement uncovered that patients with plaque rupture had more frequent positive remodeling (74.4% vs.43.2%, P=0.004), soft plaques (64.1% vs. 36.4%, P=0.012) and higher remodeling index (1.13±0.16 vs. 0.99±0.11,P=0.041) as compared with those without plaque rupture. Multivariate Logistic regression analysis showed that plasma Lp-PLA2 activity was independently associated with plaque rupture after adjusting for smoking, positive remodeling and soft plaque (Model 1: odds ratio (OR) 1.13, 95% confidence interval (CI): 1.06-1.20) or adjusting for smoking, hs-CRP level, positive remodeling and soft plaque (Model 2: OR 1.11, 95%CI: 1.04-1.1 9).Conclusions Plasma Lp-PLA2 activity is associated with plaque rupture in patients with CAD, independently of traditional CAD risk factors, hs-CRP level and IVUS parameters. Lp-PLA2 may be a risk marker for vulnerable plaques.