Background: The prognostic significance of systemic inflammatory markers in colorectal cancer (CRC) such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and modified Glasgow prognostic score (mGPS) have been well defined in literature. In addition, commonly utilized genetic markers such as combined BRAF-MMR status have also been found to be prognostic. Recent evidence suggests that the lymphocyte-to-monocyte ratio (LMR) may hold prognostic utility in CRC. However the LMR has still not been clearly defined in either its clinical utility or in comparsion to other established biomarkers. Methods: Consecutive patients from the Northern Sydney Local Health District undergoing curative surgical resection for colorectal cancer from January 1998 to December 2012 were collated. Of the 3281 patients identified, 1623 patients with complete pre-operative blood counts, BRAF-MMR IHC and clinicopathologic data were further analysed. Variables were analysed in univariate and then a multivariate cox regression model using forwards conditional method looking for association with overall survival (OS). Results: In multivariate analysis of 1623 patients, elevated LMR was associated with better overall survival (OS) (HR 0.565, 95% CI: 0.475-0.672, P < 0.001) independent of age (P < 0.001), T stage (P < 0.001), N stage (P < 0.001) and grade (P = 0.049). Other biomarkers such as NLR, PLR and combined BRAF-MMR status were not significantly associated with OS. In multivariate subgroup analysis of 389 patients with available mGPS data, LMR remained the only independently prognostic biomarker (HR 0.620, 95% CI: 0.437-0.880, p = 0.007). Conclusions: The LMR is an independent predictor of OS in CRC patients undergoing curative resection. Furthermore, the LMR appears to be superior to previously established biomarkers.