BACKGROUND: Among numerous systemic inflammatory biomarkers, it remains unclear which is the most prognostic for patients with stage II/III colon cancer. We aimed to compare the prognostic significance of systemic inflammatory biomarkers among patients with stage II/III colon cancer. METHODS: We included 1303 patients with stage II/III colon cancer who underwent potentially curative resection from July 2004 to December 2013. Sixteen systemic inflammatory biomarkers-derived from combinations of neutrophils, lymphocytes, monocytes, platelets, C-reactive protein (CRP), and albumin-were compared to identify the biomarker most associated with overall survival (OS) and disease-free survival (DFS) using receiver operating characteristic (ROC) curve analysis. RESULTS: Nine inflammatory biomarkers were predictive for OS, among which lymphocyte-to-CRP ratio (LCR), CRP-to-albumin ratio (CAR), neutrophil × CRP, monocyte × CRP, and platelet × CRP were also predictive for DFS. Among these five inflammatory biomarkers, the area under the curve (AUC) value was highest (0.630) for LCR, being significantly higher than that for neutrophil × CRP (P = 0.010), monocyte × CRP (P = 0.007), or platelet × CRP (P = 0.010) for OS. When the prognostic impact of LCR and CAR were analyzed by multivariate analysis, only LCR was an independent predictor of both OS [hazard ratio (HR), 1.77; 95% confidence interval (CI), 1.23-2.60; P = 0.002] and DFS (HR, 1.29; 95% CI, 1.00-1.66; P = 0.048). CONCLUSIONS: LCR may be the most useful predictive factor for OS and DFS in patients with stage II or III colon cancer.