Objective <p>This study aimed to evaluate the prognostic value of novel systemic inflammatory markers, particularly the Systemic Immune-Inflammation Index (SII), in predicting morbidity and mortality in patients undergoing carotid endarterectomy.</p> Methods <p>A retrospective analysis was conducted on 200 patients who underwent carotid endarterectomy. Patients were categorized into two groups based on their 1-year postoperative survival status (group-1:alive, group-2: dead). Inflammatory parameters including SII, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)were calculated. Demographic, clinical, echocardiographic, and angiographic data were analyzed. The association between inflammatory markers and outcomes was assessed using univariate and multivariate analyses.</p> Results <p>SII, NLR and PLR were significantly higher in the group-2 (<i>p</i> &lt; 0.001). Patients with internal carotid artery tortuosity exhibited longer operation times (<i>p</i> = 0.002), and those with elevated SII levels had a higher risk of adverse outcomes. No significant difference was observed in echocardiographic parameters between the two groups. The presence of comorbidities such as hyperlipidemia and coronary artery disease was also more prevalent in the group-2.</p> Conclusion <p>Systemic inflammatory markers, particularly SII, may serve as useful predictors of postoperative mortality and procedural complexity in patients undergoing carotid endarterectomy. Incorporating these markers into preoperative risk assessment may improve clinical decision-making and patient outcomes.</p> Graphical abstract <p></p>