Background <p>The triglyceride-glucose (TyG) index has demonstrated a significant association with stroke outcomes. However, its prognostic value in acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) remains inadequately explored. This study aims to evaluate the association between the TyG index and all-cause mortality in AIS patients undergoing EVT.</p> Methods <p>This was a multicenter, retrospective cohort study that included AIS patients undergoing EVT between September 2018 and January 2024. Kaplan-Meier survival analysis was performed to evaluate survival differences across TyG tertiles for both in-hospital and 90-day. Cox proportional hazards regression and restricted cubic splines (RCS) were used to examine the association between the TyG index and all-cause mortality. Additionally, interaction and subgroup analyses were conducted to evaluate the robustness and consistency of the results.</p> Results <p>Among EVT patients (median age 69 years, 56.0% male), the in-hospital and 90-day mortality rates were 7.9% and 19.1%, respectively. Cox regression analysis revealed that an elevated TyG index was significantly associated with both in-hospital mortality (adjusted hazard ratio [HR] = 1.79; 95% CI = 1.27–2.53; <i>P</i> &lt; 0.001) and 90-day mortality (HR = 1.44; 95% CI = 1.16–1.79; <i>P</i> &lt; 0.001). RCS analysis demonstrated a positive linear relationship between the TyG index and all-cause mortality. Importantly, subgroup analysis revealed that diabetes modified the relationship between the TyG index and mortality, with a stronger effect in the non-diabetic subgroup (<i>P</i> for interaction = 0.011 and 0.022, respectively).</p> Conclusion <p>The TyG index is significantly associated with all-cause mortality in non-diabetic AIS patients undergoing EVT, suggesting that it may serve as a potential evaluation tool for risk stratification in this patient population.</p> Clinical trial number <p>Not applicable.</p>