Objective: To evaluate the clinical efficacy of laparoscopic total gastrectomy with D2 lymph node dissection in treatment of advanced gastric cancer. Methods: The clinical data of 126 patients with advanced gastric cancer undergoing total gastrectomy with D2 lymph node dissection from January 2005 to December 2011 were retrospectively analyzed. Of the patients, 59 cases received laparoscopic-assisted operation (laparoscopic group) while 67 cases were subjected to open surgery (laparotomy group), and the clinical efficacies between the two groups were compared. Results: The difference in operative time and hospitalization expenses between the two groups had no statistical significance (both P>0.05), but the parameters that included time to bowel function recovery and food intake, length of postoperative hospital stay, intraoperative blood loss, and size of incision in laparoscopic group were superior to those in laparotomy group (all P<0.05). The overall incidence of postoperative complications between the two groups showed no statistical difference (P>0.05), but the incidence of surgery-related complications in laparoscopic group was lower than that in laparotomy group (P<0.05); the length of proximal or distal surgical margin, and number of resected lymph nodes of the two group were similar (all P>0.05), and the difference in 1-, 3-, 5-year overall survival or free tumor survival between the two groups showed no statistical significance (all P>0.05). Conclusion: Laparoscopic total gastrectomy with D2 lymph node dissection for advanced gastric cancer is safe and effective.