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Purpose: Many systemic inflammatory markers have been identified to be prognostic factors in various diseases, including colorectal cancer (CRC). The Colon Inflammatory Index (CII), which is based on the lactate dehydrogenase (LDH) level and the neutrophil-to-lymphocyte ratio (NLR), is reportedly a predictor of the outcome of chemotherapy in patients with metastatic CRC. This retrospective review study aimed to determine whether CII can predict the prognosis after surgical resection of CRC. Methods: A total of 1,273 patients who underwent CRC resection were enrolled and divided into a training cohort (n = 799) and a validation cohort (n = 474). The impact of the preoperative CII score on overall survival (OS) and recurrence-free survival (RFS) was assessed. Results: In the training cohort, the CII score was good in 569 patients (71.2%), intermediate in 209 (26.2%), and poor in 21 (2.6%). There were significant between-group differences in body mass index, American Society of Anaesthesiologists physical status, and preoperative tumour markers. The 5-year OS rate was significantly lower in patients with an intermediate or poor CII score (CII risk) than in those with no CII risk (73.8% vs. 84.2%; p < 0.001, log-rank test). In multivariate analysis, CII risk remained a significant independent predictor of poor OS (hazard ratio 1.75; 95% confidence interval 1.18–2.60; p = 0.006). In the validation cohort, the 5-year OS rate was significantly lower in patients with CII risk than in those with no CII risk (82.8% vs. 88.4%; p = 0.046, log-rank test). Conclusion: These findings indicate that the CII can predict OS after resection of CRC. [ABSTRACT FROM AUTHOR]