AIM: To investigate the relationship between serum soluble growth stimulation expressed gene 2 protein(sST2) level and coronary artery complex lesions and their severity. METHODS: A total of 430 patients, who were sequentially admitted to hospital for selective coronary artery angiography, were divided into control group (non-coronary heart disease group, 136 patients), simple lesions group of coronary heart disease (86 patients), complex lesions group (208 patients). To quantitative evaluate the complexity of coronary artery lesions, Syntax scores were further performed on patients in complex lesions groups, including 139 patients in the low-risk group, 36 patients in the medium-risk group, and 33 patients in the high-risk group. The serum soluble ST2 level of each group of patients was tested by means of ELISA. Spearman correlation analysis was used for the correlation between the level of soluble ST2 and the severity of coronary complex lesions. RESULTS: In 430 subjects, the soluble ST2 level of all patients with coronary heart disease (including simple lesions and complex lesions) was significantly higher than that of the control group [(3 449±1 250) vs. (2 743±961) pg/mL, P<0.001]; the sST2 levels of patients in the coronary artery simple lesions group, complex lesions low-risk group, medium-risk group and high-risk group were (3 200±1 406), (3 338±1 064), (3 728±1 228) and (4 261±1 235) pg/mL respectively, and the differences of sST2 levels among above four groups were statistically significant (P<0.001). Logistic regression analysis showed that sST2 was independently associated with coronary heart disease (OR=1.001, P<0.001) and sST2 was independently associated with the severity of coronary artery complex lesions (OR=1.001, P<0.001). Spearman-related analysis shows that the expression levels of sST2 are positively related to the severity of coronary artery lesions (rs: 0.543, P<0.001). The ROC curve showed that the area under the curve of sST2 for complex coronary lesions was AUC=0.726. CONCLUSION: Serum soluble ST2 level may be an important predictor of complicated coronary artery disease.