Aim To evaluate the value and correlation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and homocysteine (Hcy) combined detection for coronary atherosclerotic plaque in patients with coronary heart disease (CHD). Methods According to clinical classification, 188 patients with CHD were divided into 2 groups:stable angina pectoris (SAP) group (n＝106), acute coronary syndrome (ACS) group (n＝82); Those who had normal coronary angiography at the same time were selected as control group (n＝90). Serum levels of NT-proBNP, Hcy and high-sensitivity C-reactive protein (hs-CRP) were measured. According to the results of coronary angiography, Gensini score was calculated. Plaque component index was detected by intravascular ultrasound. Correlations between NT-proBNP, Hcy levels and Gensini score, plaque composition index were analyzed by Pearson correlation analysis. Relationship between NT-proBNP, Hcy levels and vulnerable plaques was analyzed by Logistic regression analysis. The values of NT-proBNP and Hcy in predicting vulnerable plaques were evaluated by the receiver operating characteristic (ROC) curve area under curve (AUC). Results There were significant differences in the concentrations of NT-proBNP, Hcy and hs-CRP among the 3 groups (P＜0.05), and all of them were ACS group＞SAP group＞control group (P＜0.05). The Gensini score, the ratio of necrotic core (NC), vascular remodeling index (VRI) and plaque eccentricity index (PEI) in group ACS were significantly higher than those in SAP group (P＜0.05). The levels of NT-proBNP and Hcy were positively correlated with Gensini score and plaque NC ratio, VRI and PEI (all P＜0.05). Multivariate Logistic regression analysis showed that serum NT-proBNP and Hcy levels were independent risk factors for vulnerable plaques in patients with CHD (all P＜0.05). The AUC values of NT-proBNP and Hcy in predicting coronary vulnerable plaques were 0.764 (95%CI 0.729~0.803, P＝0.021), 0.779 (95%CI 0.742~0.814, P＝0.015). When NT-proBNP and Hcy were combined, the AUC of predicting coronary vulnerable plaques was 0.886 (95%CI 0.823~0.951, P＝0.004). Conclusion Combined detection of serum NT-proBNP and Hcy can effectively assess coronary atherosclerotic plaques in patients with CHD.