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The aim of the study was to evaluate the oncological outcomes of complete mesocolic excision (CME) in colon cancer patients.CME is considered a standard procedure for colon cancer patients. However, previous evidence regarding the effect of CME on prognosis has fundamental limitations that prevent it from being fully accepted.Patients who underwent radical resection for colon cancer were enrolled between November 2012 and March 2016. According to the principles of CME, patients were stratified into 2 groups based on intraoperative surgical fields and specimen photographs. The primary outcome was local recurrence-free survival (LRFS). The clinicopathological data and follow-up information were collected and recorded. The final follow-up date was April 2016. The trial was registered in ClinicalTrials.gov (identifier: NCT01724775).There were 220 patients in the CME group and 110 patients in the noncomplete mesocolic excision (NCME) group. Baseline characteristics were well balanced. Compared with NCME, CME was associated with a greater number of total lymph nodes (24 vs 20, P = 0.002). Postoperative complications did not differ between the 2 groups. CME had a positive effect on LRFS compared with NCME (100.0% vs 90.2%, log-rank P < 0.001). Mesocolic dissection (100.0% vs 87.9%, log-rank P < 0.001) and nontumor deposits (97.2% vs 91.6%, log-rank P < 0.022) were also associated with improved LRFS.Our findings demonstrate that, compared with NCME, CME improves 3-year LRFS without increasing surgical risks.