BackgroundThe triglyceride-glucose (TyG) index was significantly associated with insulin resistance (IR). Several studies have validated the effect of TyG index on cerebrovascular disease. However, the value of TyG index in patients with severe stroke requiring ICU admission remains unclear. The aim of this study was to investigate the association between the TyG index and clinical prognosis of critically ill patients with ischemic stroke (IS).MethodsThis study identified patients with severe IS requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-IV) database, and divided them into quartiles based on TyG index level. The outcomes included in-hospital mortality and ICU mortality. The association between the TyG index and clinical outcomes in critically ill patients with IS was elucidated using Cox proportional hazards regression analysis and restricted cubic splines.ResultsA total of 733 patients (55.8% male) were enrolled. The hospital mortality and intensive care unit (ICU) mortality reached 19.0% and 14.9%, respectively. Multivariate Cox proportional hazards analysis showed that the elevated TyG index was significantly related to all-cause death. After confounders adjusting, patients with an elevated TyG index had a significant association with hospital mortality (adjusted hazard ratio, 1.371; 95% confidence interval, 1.053–1.784; P = 0.013) and ICU mortality (adjusted hazard ratio, 1.653; 95% confidence interval, 1.244–2.197; P = 0.001). Restricted cubic splines revealed that a progressively increasing risk of all-cause mortality was related to an elevated TyG index.ConclusionThe TyG index has a significant association with hospital and ICU all-cause death in critically ill patients with IS. This finding demonstrates that the TyG index might be useful in identifying patients with IS at high risk of all-cause death.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12933-023-01864-x.