BACKGROUNDInflammatory markers for the prognosis of acute ischemic stroke (AIS) with endovascular therapy remain unclear. The purpose of this study was to investigate the association between the Systemic Inflammatory Response Index (SIRI) and Neutrophil-to-Lymphocyte Ratio (NLR) with unfavorable functional outcomes at 90-day in individuals of AIS who underwent endovascular therapy. METHODS128 AIS patients who had endovascular therapy were enrolled from the Nanjing Stroke Registry between September 2019 and November 2022. Peripheral venous blood was collected from patients within 24 h of admission for information on the following parameters: neutrophil count, lymphocyte count, monocyte count. Then, the SIRI and NLR values were calculated, and the association among SIRI, NLR, and modified Rankin Scale (mRS) scores 90 days after endovascular therapy was examined via univariate and multivariate logistic analyses. ROC curves were utilized to determine the best threshold for SIRI and NLR in predicting negative neurological outcomes following endovascular treatment for patients with AIS. RESULTS128 participants were evaluated, among which 50% had unfavorable outcomes. Linear regression analysis showed that the best threshold for SIRI was >1.407 (OR = 1.265; 95% CI, 1.071-1.493; P = 0.006), and for NLR it was >5.347 (odds ratio; OR = 1.088; 95% confidence interval [CI], 1.007-1.175; P = 0.033). These results revealed NLR and SIRI as significant predictors of unfavorable outcomes at 90 days. The AUC for SIRI and NLR in predicting 90-day adverse outcomes was 0.643 and 0.609, respectively. CONCLUSIONSHigher SIRI and NLR levels at admission may lead to unfavorable outcomes at 90 days for AIS patients with endovascular therapy.