Abstract: Objective To explore the risk factors of coronary heart disease with multiple coronary artery lesions. Methods Six hundred and seventy-two acute coronary syndrome (ACS) patients who underwent coronary angiography (CAG) in Chinese PLA General Hospital were divided into multiple-vessel disease group and one-vessel disease group according to CAG result. Their clinical baseline data were analyzed retrospectively. The correlation between cardiovascular risk factors and the severity of coronary artery lesions was analyzed. Logistic regression was performed to analyze the independent risk factors of multiple-vessel coronary artery disease. Results Univariate analysis showed that patients who were older, with higher level of SBP/DBP, hypertension, diabetes mellitus or complicated with hypertension and diabetes mellitus were more likely to be in multiple-vessel disease group (P< 0.05). Logistic regression revealed hypertension (OR=1.519, P=0.016) and diabetes mellitus (OR=1.680, P=0.007) were independent risk factors of coronary multivessel lesions. Furthermore, patients with hypertension complicated with diabetes mellitus could raise the risk (OR=1.839, P=0.005). Conclusion This study suggests that hypertension, diabetes mellitus are the predictors of multiple-vessel coronary artery disease, and the incidence of multiple-vessel disease will be higher resulting from the interaction of hypertension and diabetes mellitus.