Objective To investigate the relationship of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and the characteristics of coronary artery plaque among the patients of coronary heart disease. Methods A total of 165 patients with coronary heart diseases who underwent coronary angiography (CAG) and intravascular ultrasound (IVUS) in our 2 departments from July 2015 to July 2016 were enrolled in this study. According to the findings, the patients were divided into stable plaque group (n=86) and vulnerable plaque group (n=79). The biochemical indicators, parameters of IVUS and serum Lp-PLA2 level were observed, and correlation between Lp-PLA2 and plaque features were analyzed. SPSS statistics 17.0 was used to perform the statistical analysis. Student′s t test or Chi-square test was employed for the comparison between the 2 groups. Pearson linear correlation analysis was used for single factor analysis, and logistic regression analysis was adopted for the risk factors affecting plaque stability. Results Compared with the stable plaque group, the vulnerable plaque group had higher plaque burden [(58.20±13.59)% vs(54.72±9.98)%], vascular remodeling index [(1.61±0.32) vs (1.13±0.26)], and plaque eccentricity index [(1.58±0.15) vs (1.48±0.36)], larger percentages of necrotic tissue [(25.1±9.9)% vs (12.3±7.5)%] and calcified tissue [(6.5±3.5)% vs (0.8±0.4)%], thinner fibroatheroma cap thickness [(0.60±0.27) vs (0.75±0.31) mm] and lower percentages of fibro-lipid tissue [(17.0±5.6)% vs (20.2±6.1)%] and fibrous tissue [(59.9±7.5)% vs (62.2±7.1)%] (all P<0.05). The serum level of Lp-PLA2 was positively correlated with percentage of plaque necrotic tissue (r=0.514), plaque burden (r=0.395), vascular remodeling index (r=0.832), plaque eccentricity index (r=0.904), but negatively with fibroatheroma cap thickness (r=-0.710) (all P<0.01). The significant risk factors for plaque stability were hypertension (OR=6.82,5%CI 2.16-21.46, P=0.01), diabetes mellitus (OR=2.65,5%CI 1.02-6.74, P=0.04), history of smoking (OR=1.25,5%CI 1.06-1.62, P<0.01), and serum levels of LDL-L (OR=1.36,5%CI 1.10-1.76, P<0.01) and Lp-PLA2 (OR=10.69,5%CI 11.72-66.91, P=0.001). Conclusion The serum Lp-PLA2 level can be used as a sensitive index in evaluation of the instability of coronary artery plaque.