The role of inflammation in the pathophysiology of atherosclerosis is extensive. Our study aims to assess the predictive role of inflammatory indexes regarding in-hospital mortality in major vascular surgery of Leriche syndrome as a convenient, low-cost, and noninvasive prognostic marker to optimize the patient's perioperative course. : Our retrospective single-center study enrolled consecutive patients diagnosed with aortoiliac occlusive disease, Leriche syndrome, who underwent elective major vascular surgery between 2017 and 2023 in a tertiary cardiovascular center. Preoperative, postoperative, and day-one after-surgery data, including systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and monocyte-lymphocyte ratio, were studied to the endpoint, in-hospital death. We also tested the delta values of the indexes to the endpoint. The indexes were compared to the Revised Cardiac Risk Index (RCRI) and Vascular Surgery Group Cardiac Risk Index (VSG-CRI) for outcome prediction. The tested inflammatory indexes significantly increased from the preoperative to postoperative and, further, to the day-one settings. Preoperative AISI ( = 0.040) emerged as the only independent risk factor regarding in-hospital death occurrence in Leriche patients who underwent major revascularization surgery. While RCRI did not significantly predict the endpoint (AUC = 0.698, = 0.057), VSG-CRI (AUC = 0.864, = 0.001) presented the best result in ROC analysis. Postoperative NLR (AUC = 0.758, = 0.006) was next, followed by NLR postoperative-preoperative (_Preop-_Postop) delta value (AUC = 0.725, = 0.004), postoperative SIRI (AUC = 0.716, = 0.016), SIRI_Preop-_Postop delta value (AUC = 0.712, = 0.016), postoperative SII (AUC = 0.692, = 0.032), and SII_Preop-_Postop delta value (AUC = 0.631, = 0.030). : Inflammatory indexes are valuable tools for assessing perioperative risk in major vascular surgery, enhancing the value of the already validated risk scores.