Objective To analyze the short-term efficacy of laparoscopic-assisted D2 radical surgery combined with complete mesogastric excision (CME) in the treatment of advanced gastric cancer.Methods The clinical data of 80 patients with advanced gastric cancer admitted to our hospital from February 2018 to January 2019 were retrospectively analyzed. According to different surgical methods, 40 patients who underwent laparoscopic-assisted D2 radical resection were included in the D2 group, and the rest forty patients who underwent laparoscopic-assisted D2 radical resection plus CME surgery were included in the CME+D2 group. The surgery-related indicators, Generic Quality of Life Inventory-74 (GQOLI-74) score, complication rate, tumor recurrence rate, metastasis rate, and the survival rate were compared between the groups.Results Compared with D2 group, the operative duration and length of hospital stay were shorter, intraoperative blood loss was less and the number of lymph node dissections was fewer in the CME+D2 group (P <0.05). There was no difference in the time to pass gas after surgery, complication rate, or 6-month survival rate, tumor recurrence rate and metastasis rate between the two groups (P > 0.05). The 1-year survival rate was higher but the metastasis rate was lower in the CME+D2 group than in the D2 group (P <0.05). However, 1-year tumor recurrence rate was not different between the groups (P > 0.05). The post-surgery GQOLI-74 scores in the CME+D2 group were higher than those in D2 group, though they were improved in both groups in relative to GQOLI-74 scores prior to the surgery (P <0.05). Besides, preoperative GQOLI-74 scores did not differ between the two groups (P > 0.05).Conclusions Laparoscopic-assisted D2 radical surgery combined with CME is conducive to complete lymph node dissection, reduces operative duration and intraoperative blood loss, promotes postoperative recovery and improves the quality of life for patients with advanced gastric cancer. It has fewer postoperative complications and is more feasible in the treatment of advanced gastric cancer compared with laparoscopic-assisted D2 radical surgery alone.