Background: The prevalence of colon carcinoma is fairly limited in Egypt, but it has a high fatality incidence. Colon carcinoma is a significant public health issue globally. Objectives: This study aimed to determine if complete mesocolic excision (CME) with main vessel ligation approach yields an oncologically better outcome in terms of lymph nodes and safety margins compared to traditional operation for colon carcinoma. Patients and methods: A prospective observational research that was conducted in the General Surgery Department of the Assiut University Hospitals between 2019 and 2021. Results: Twenty-nine patients performed conventional surgery (non-CME group) and other twenty-nine patients performed CME with sharp separation of the supplying vasculature's (central vessel ligation, CVL) and the embryological planes (CME group). Substantially improved outcomes were noted regarding safety margin clearance and lymph node output (CME group: 22.5 vs. non-CME group:12, P<0.0001) and lymph node ratios (CME group: 0.03 vs. non-CME group: 0.22; P<0.0001). Conclusion: When carried out in accordance with the right embryological plans and by trained practitioners, CME seems to be a safe therapy. The lymph node ratios are also affected since it offers superior specimens with a larger lymph node output. Therefore, it should be researched and implemented more often to use CM with CVL.