Objective To evaluate the impact of cholesterol， high-density lipoprotein， and glucose （CHG） index levels on progressive ischemic stroke（ PIS）， so as to provide evidence and guidance for the comprehensive management of blood lipids and blood glucose in patients with PIS. Methods This study was a retrospective study. A total of 1 356 patients primarily diagnosed with ischemic stroke at Cangzhou People's Hospital from January 2019 to December 2024 were included as the research subjects. According to whether the National Institute of Health Stroke Scale（ NIHSS） score increased by ≥ 2 compared to admission score within 7 days after onset， patients were divided into a progressive group（ NIHSS score increased by ≥ 2 compared to admission score） and a non-progressive group. The correlation between the CHG index and PIS was investigated using the Logistic regression， receiver operating characteristic（ ROC） curve， and subgroup analysis. Results During hospitalization of 1 356 patients， a total of 375 patients experienced PIS. The age， baseline NIHSS score， proportion of atrial fibrillation history， fasting blood glucose， glycated hemoglobin， total cholesterol， low-density lipoprotein cholesterol， CHG index of progressive group were all higher than those of non-progressive group， and the differences were statistically significant（ all P＜0.05）. After adjusting for confounding factors with P ＜ 0.05 in univariate Logistic regression analysis using multivariate Logistic regression， the results showed that the CHG index［ OR=1.532， 95%CI（ 1.206，1.945）， P＜0.001］ remained an independent risk factor for PIS. Subgroup analysis revealed that the CHG index was positively associated with PIS risk in male gender［ OR=1.589， 95%CI（ 1.225，2.061）， P＜0.001］， female gender［ OR=1.970， 95%CI （1.460，2.658）， P＜0.001］， no history of smoking［ OR=1.870， 95%CI（ 1.491，2.346）， P＜0.001］， no history of alcohol consumption［ OR=1.806， 95%CI（ 1.460， 2.235）， P＜0.001］， history of hypertension［ OR=1.783， 95%CI（ 1.428，2.227）， P＜0.001］， no history of hypertension［ OR=1.555， 95%CI（ 1.068，2.264）， P=0.021］， history of diabetes［ OR=2.093， 95%CI（ 1.507，2.907）， P ＜ 0.001］， no history of diabetes［ OR=1.584， 95%CI（ 1.229，2.042）， P＜ 0.001］， history of coronary heart disease［ OR=1.457， 95%CI（ 1.032，2.058）， P=0.033］， no history of coronary heart disease［ OR=1.851， 95%CI（ 1.471， 2.329）， P＜ 0.001］， no history of cerebral infarction［ OR=1.739， 95%CI（ 1.430， 2.116）， P＜0.001］， history of peripheral vascular disease ［OR=3.869， 95%CI（ 2.002，7.478）， P＜ 0.001］， and no history of peripheral vascular disease［ OR=1.570， 95%CI（ 1.284， 1.921）， P ＜ 0.001］. Significant interaction effects were observed in the subgroups classified by TOAST（ Pinteraction ＜ 0.001）. The area under the ROC curve was 0.696. Conclusions A high CHG index is significantly associated with an increased risk of PIS.