Purpose <p>To explore the application effect of the technique of “priority dissecting of the inferior mesenteric artery combined with complete medial approach (IMA-CMA)” in laparoscopic left-sided colon cancer radical resection.</p> Methods <p>A total of 99 patients who underwent laparoscopic left-sided colon cancer radical resection with splenic flexure mobilization between September 2021 to May 2023 were included. Sixty-eight of these patients were analyzed after propensity score matching (PSM). The perioperative characteristics were compared.</p> Results <p>Among these enrolled patients, 45 underwent the traditional approach, and 54 underwent IMA-CMA approach. After PSM, the patients were matched to include 34 patients in each group, with no significant differences in the sex (<i>p</i> = 0.618) or location of tumor (<i>p</i> = 0.798) between the two groups. The patients in IMA-CMA group had shorter operating time (<i>p</i> = 0.032), less intraoperative blood loss (<i>p</i> = 0.003), a higher number of harvested lymph nodes (<i>p</i> = 0.044) and center group lymph nodes(<i>p</i> = 0.037), and a shorter postoperative hospital stay (<i>p</i> = 0.011). Number of positive lymph nodes and postoperative complications were not significantly different between the two groups.</p> Conclusions <p>The technique of IMA-CMA for splenic flexure mobilization is safe and feasible. It can reduce operating time, intraoperative blood loss and postoperative hospital stay, which is conducive to achieving a thorough D3 lymphadenectomy without increasing the incidence of perioperative complications.</p>