Abstract The colonic microbiome has been implicated in the pathogenesis of colorectal cancer (CRC) and intestinal microbiome alterations are not confined to the tumour. Since data on whether the microbiome normalises or remains altered after resection of CRC are conflicting, we studied the colonic microbiota of patients after resection of CRC. We profiled the microbiota using 16S rRNA gene amplicon sequencing in colonic biopsies from patients after resection of CRC (n = 63) in comparison with controls (n = 52), subjects with newly diagnosed CRC (n = 93) and polyps (i = 28). The colonic microbiota after surgical resection remained significantly different from that of controls in 65% of patients. Genus-level profiling and beta-diversity confirmed two distinct groups of patients after resection of CRC: one with an abnormal microbiota similar to that of patients with newly diagnosed CRC and another similar to non-CRC controls. Consumption levels of several dietary ingredients and cardiovascular drugs co-varied with differences in microbiota composition suggesting lifestyle factors may modulate differential microbiome trajectories after surgical resection. This study supports investigation of the colonic microbiota as a marker of risk for development of CRC.