Objective <p>To evaluate the short- and long-term outcomes of totally laparoscopic, laparoscopic-assisted, and open total gastrectomy in gastric cancer patients after neoadjuvant therapy.</p> Methods <p>This multicenter retrospective cohort study was conducted to collect clinical data from 289 patients who underwent total radical gastrectomy after neoadjuvant therapy at five centers. The patients were divided into three groups according to the surgical method they received: totally laparoscopic, laparoscopic-assisted, and open groups. The general baseline data, intraoperative and postoperative conditions, postoperative histopathological results, related complications, and survival outcomes of the three groups were compared.</p> Results <p>The totally laparoscopic group had a longer operation time and more intraoperative blood loss than the laparoscopic-assisted and open groups. However, the first postoperative bowel movement, first postoperative defecation, first postoperative meal, and removal of the postoperative drainage tube occurred earlier, and the total number of lymph node dissections was higher in totally laparoscopic group. The intraoperative blood transfusion rate, postoperative intensive care unit admission rate, maximum tumor diameter, positive lymph node dissection number, tumor staging, and hospitalization time did not differ significantly among the three groups, nor did the total incidence of postoperative complications, Clavien-Dindo classification, 30- and 90-day readmission rates and survival outcomes (all <i>p</i> &gt; 0.05).</p> Conclusion <p>For patients with gastric cancer treated with neoadjuvant therapy, the three surgical approaches showed no significant differences in both short- and long-term outcomes.Although totally laparoscopic total gastrectomy has a longer operation time, it has the advantages of faster postoperative recovery and earlier food intake.</p>