Prognosis in colon cancer is based on pathological criteria including TNM staging. However, there are deficiencies in this approach, and the lymph node ratio (LNR) has been proposed to improve the prediction of outcomes. LNR is dependent on optimal retrieval of lymph nodes-lymph node count (LNC). Recent studies have suggested that an elevated preoperative systemic inflammatory response (SIR) was associated with a lower LNC and a higher LNR. However, there are a number of potential confounding factors. The aim of the present study was to examine, in detail, these relationships in a large cohort of patients.A prospectively maintained database of all patients undergoing colon cancer resection in our institution was examined. The SIR was measured by a number of inflammatory markers and their scores: modified Glasgow Prognostic Score (mGPS) (C-reactive protein/albumin), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and lymphocyte monocyte ratio (LMR) using standard thresholds. The relationships between LNC and LNR, and clinicopathological characteristics (including the mGPS, NLR, PLR, and LMR) were examined using chi-square test for trend and binary logistic regression analysis, where appropriate.Of the 896 patients included in the study, 418 (47%) were male, the median LNC was 17 (1-71), and the median LNR in node positive disease was 0.16 (0.03-1). On multivariate analysis, there was a significant independent relationship between an elevated LNC (≥12) and laparoscopic surgery (P < .001), right-sided tumors (P < .001), later date of resection (2007-2016) (P < .001), T stage (P < .001), and venous invasion (P < .001). In those patients with a LNC ≥12 and node-positive disease (n = 272), on multivariate analysis, there was a significant relationship between an elevated LNR (≥0.25), and T stage (P < .01) and differentiation (P < .05). Finally, in patients with node-positive disease who had surgery later (2007-2016), LNR was directly superior to N stage for both cancer-specific survival (LNR: hazard ratio [HR] 2.62, 95% confidence interval [CI] 1.25-5.52, P = .011) and overall survival (LNR: HR 2.02, 95% CI 1.12-3.68, P = .022).Neither LNC nor LNR was associated with markers of the SIR; however, LNC and LNR were directly associated. In high-quality surgical and pathological practice, LNR had superior prognostic value compared with N stage in patients undergoing surgery for colon cancer.