Background. Our aim was to compare the emerging technique of single-incision laparoscopic surgery complete mesocolic excision (SILS CME) colectomy with the standard multiport laparoscopic CME (MPL CME) colectomy. Methods. MEDLINE (PubMed), Scopus, EMBASE, Ovid, and the Cochrane library were searched. Studies comparing the SILS CME with MPL CME in adults with colon adenocarcinoma were included. The Jadad and Newcastle Ottawa Scales were used to critically appraise the studies. The presence of statistical heterogeneity or publication bias was examined. Results. Seven studies (3 randomized) with a total number of 1344 patients were included (546 SILS CME and 798 MPL CME). No difference was found in anastomotic leakage (odds ratio [OR] = 0.79 [0.31 to 2.03]; P = .63), number of lymph nodes (weighted mean difference [WMD] = 0.85 [−0.97 to 2.66]; P = .36), hospital stay (WMD = 0.01 [−0.19 to 0.20]; P = .96), overall survival (hazard ratio [HR] = 1.19 [0.29 to 4.80]; P = .81), and disease-free survival (HR = 1.30 [0.30 to 5.61]; P = .72). Skin incision was shorter in SILS CME group (WMD = −3.02 [−3.25 to −2.80]; P < .00001) but with no difference in pain reported in postoperative day 1 (standardized mean difference [SMD] = −0.21 [−0.50 to 0.09]; P = .17) or day 2 (SMD = 0.16 [−0.52 to 0.84]; P = .64). Conclusions. SILS CME, although technically more demanding, has equivalent short- and long-term outcomes when compared with MPL CME. Potential benefits in cosmesis or postoperative pain need to be further explored by high-quality randomized controlled trials.