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Background The decision of ligation at the origin of the inferior mesenteric artery (IMA) or below the origin of the left colic artery (LCA) has remained a dilemma for surgeons in colorectal cancer surgery. The available studies are controversial. The objective of this meta-analysis is to compare the predictive significance of high versus low ligation in colorectal cancer surgery. Methods A literature search done using Medline, EMBASE, GoogleScholar, and references. A meta-analysis was performed to analyze the 5-year overall survival (OS) of the high and low ligation using hazard ratio (HR) and 95% confidence interval (CI). We further analyzed 2 subgroups considering the level of lymph nodes (LNs) extension. That is IMA positive (+ve) and negative (-ve) LNs. Survival differences were analyzed. Results A total of 3119 patients in 5 cohorts were included in this meta-analysis. The pooled HR results showed significant OS benefit of high ligation than low ligation (HR; 0.77, 95% CI: 0.66-0.89) in the "IMA +ve" group with 33% decreased risk, while there is no statistical significance in the "IMA -ve" (HR 0.66, 95% CI: 0.30-1.46) and the "all cases" group (HR 0.69, 95% CI: 0.41-1.15). Conclusion The pooled data showed high ligation of IMA has a better survival benefit for the patients with IMA positive LNs. It signifies high ligation should be recommended for the advanced cases or with the suspected high risk of IMA lymphatic metastasis. The limited number of articles demands future high-powered, well-designed randomized controlled trials (RCTs) for the further reliable conclusion.