High-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) have been reported to be independent predictors of atherosclerosis. However, whether the combination of these two markers can improve theprediction of atherosclerosis is unknown. This study aimed to evaluate the association between combining hs-CRP and Lp-PLA2 and predicting carotid atherosclerosis. A total of 1982 participants aged >= 40 years were included in this study. Hs-CRP and Lp-PLA2 were measured by a high-sensitivity nephelometry assay and quantitative sandwich enzyme-linked immunosorbent assay, respectively. Ultrasonography was performed on the bilateral carotid arteries to evaluate stenosis and plaques. Multivariable logistic regression models were used to analyse the association between the combination of the hs-CRP and Lp-PLA2 levels and carotid plaques and stenosis. A total of 1579 (79.7%) and 181 (9.1%) subjects had carotid plaques and carotid stenosis, respectively. The group with high hs-CRP and Lp-PLA2 levels had the highest prevalence of carotid plaques (90.6%) and stenosis (20.8%). A significant association was found between high hs-CRP and Lp-PLA2 levels and carotid stenosis (adjusted odds ratio [OR]: 2.39; 95% confidence interval [CI]: 1.13-5.09), but this combination was not associated with carotid plaques (OR: 2.62, 95% CI: 0.93-7.38). The results suggested that the combination of hs-CRP and Lp-PLA2 were better predictors than either protein alone with regard to carotid atherosclerosis.