Background: Evidence from clinical trials and cohort studies suggest primary tumour location is a prognostic factor in patients with advanced colorectal cancer and that right and left colonic tumours should be considered as distinct clinical and biological entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), and cancer-specific survival (CSS) in patients undergoing surgery for colon cancer. Methods: Clinicopathological characteristics were extracted from a prospective database of patients who underwent potentially curative surgery for colon cancer between 1997 and 2016, at a single centre. The tumour microenvironment was assessed retrospectively using routine H&E pathological sections. Results: 722 patients were included. The majority of patients were over the age of 65 years (69%), were male (52%), had right-sided (RS) tumour location (63%), had TNM stage I/II disease (64%) and 25% received adjuvant chemotherapy. RS location was associated with poor tumour differentiation (p =< 0.001) and high venous invasion (p =0.003) but not with TNM stage (p= 0.310), perineural invasion (p= 0.286), tumour budding (p= 0.568), margin involvement (p= 0.424), peritoneal involvement (p= 0.689), tumour necrosis (p= 0.423) or tumour cell proliferation (p= 0.605). RS location was not associated with tumour inflammatory cell infiltrate at the margin (CD3⁺p= 0.103, CD8⁺p= 0.620) or in the tumour (CD3⁺p= 0.540, CD8⁺p= 0.713) or with tumour stroma percentage (p= 0.843). RS location was associated with high mGPS (p =0.007) and neutrophil:platelet score (p =0.001) but not NLR (p= 0.387). Finally, there was no difference between RS and left sided tumour location in the administration of adjuvant chemotherapy (p= 0.901) or CSS (p= 0.951). Conclusions: Few clinicopathological features were associated with tumour location in patients undergoing surgery for colon cancer. However, RS tumour location was consistently associated with a higher SIR. This may account for the poor prognosis associated with RS tumours in patients with advanced colon cancer.