Background A low high-density lipoproteincholesterol (HDL-C) to apolipoprotein A-I (apoA-I) ratio which reflects a small HDL-C particle size is emerging as an important predictor of cardiovascular risks.This study aimed to determine the association of HDL-C/apoA-I ratio with the severity of coronary artery lesions in diabetic patients.Methods Observational study was conducted and 478 diabetic patients with acute coronary syndrome (ACS) were enrolled.Baseline serum levels of HDL-C,apoA-I,clinical and biochemical parameters were collected.All patients underwent coronary angiography to evaluate the severity of coronary artery disease (CAD) in terms of the number of stenotic coronary arteries (defined as a stenosis ≥50％) and the calculated Gensini score.Patients were then divided into different subgroups according to the two categories: single-,double-or triple-vessel groups;and Gensini Score groups (lower ≤4,middle: 5-15,and upper ≥16).Receiver operating characteristic curves (ROC) were conducted to evaluate the diagnostic values in identifying severe CAD lesions.The association between HDL-C/apoA-I ratio and CAD severity was determined by multivariate logistic regression analysis.Results Patients with triple-vessel lesions or upper Gensini score had more CAD risk factors such as older age,smoking,low HDL-C and elevated fasting blood glucose (FBG).A lower HDL-C/apoA-I ratio corresponded to more vessels stenoses and a higher Gensini score.Notably,HDL-C/apoA-I outperformed HDL-C or apoA-I alone in diagnosing severe CAD lesions in ROC analyses.Moreover,multivariate regression analyses revealed that after adjustment for traditional risk factors such as LDL-C,FBG and HAb1c,HDL-C/apoA-I ratio remained independently associated with the severity of CAD in diabetic patients with ACS (all P＜0.05).Conclusions HDL-C/apoA-I may be a useful indicator for the severity of CAD in diabetic patients with ACS.