AbstractAimsThe prognosis of colorectal cancer (CRC) has been historically reliant on the Tumor Node Metastasis (TNM) staging system, but there is variability in outcomes among patients at similar stages. Therefore, there is an urgent need for more robust biomarkers. The aim of this study was to assess the clinical feasibility of the recently reported Inflammatory Burden Index (IBI) for predicting short‐ and long‐term outcomes in patients with CRC.MethodsThis was a retrospective observational study of 555 CRC patients undergoing surgery for primary tumor resection. We determined the prognostic value of preoperative IBI for disease‐free and overall survival, and its predictive value for perioperative risk of infectious complications, including surgical site infection.ResultsIncreased preoperative IBI was significantly associated with advanced disease stage and poor oncological outcome in CRC patients. Higher IBI was independently linked to poorer disease‐free and overall survival. Similar outcomes were observed in a subanalysis focused on high‐risk stage II and stage III CRC patients. Elevated preoperative IBI was significantly correlated with an increased risk of surgical site infection and other postoperative infectious complications. Propensity score‐matching analysis validated the impact of IBI on the prognosis in CRC patients.ConclusionWe established preoperative IBI as a valuable predictive biomarker for perioperative risks and oncological outcomes in CRC patients. Preoperative IBI is useful for designing effective perioperative management and postoperative oncological follow‐up.