Aim To investigate the relationship between serum phospholipid transfer protein (PLTP) activity levels and severity of coronary artery lesions in patients with coronary heart disease (CHD). Methods 202 patients with chest pain were recruited in the Xishan People’s Hospital of Wuxi from June 2015 to June 2016, and these patients were divided into two groups based on coronary angiography (CHD group and non-CHD group). PLTP activity was measured with an assay kit, and the severity of coronary artery disease assessed by Gensini score was analyzed. Results PLTP activity levels and Gensini score in CHD group were significantly higher than that in non-CHD group (90.3(67～118)mg/dL vs 77.4 (54.6～103.3)mg/dL, P<0.05; 29(8～48) vs 2(0～6), P<0.001). PLTP activity levels and Gensini score were higher in patients aged 70～79 years old,male and diabetes than patients aged 60～69 years old, female and non-diabetes. Multiple linear regression analysis showed that PLTP activity levels were predictor for Gensini score after adjusting for the other risk factors (Beta=0.356, P<0.001). ROC curve was for PLTP activity levels to detect CHD patients with upper Gensini score quartile, and the area under the curve was 0.749(P<0.001). Conclusion Serum PLTP activity levels were predictive for the severity of coronary artery lesions in patients with CHD.