Objective: To explore the feasibility, safety and long-term efficacy of laparoscopic total gastrectomy combined with distal pancreaticosplenectomy for the treatment of T4b gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of consecutive patients with T4b gastric cancer invading pancreatic tail undergoing laparoscopic or open total gastrectomy combined with distal pancreaticosplenectomy from January 2010 to December 2014 were analyzed retrospectively. Enrollment criteria: (1) primary gastric cancer confirmed by pathology as T4b adenocarcinoma; (2) chest+abdominal+pelvic enhanced CT indicated cancer invading pancreatic tail without distant metastasis, and R0 resection was evaluated as feasible before operation; (3) physical status was ECOG score 0 to 2, and was tolerant to operation. Patients with peritoneal implant metastasis and tumor invasion of other organs during operation, or changes in surgical methods for other reasons were excluded. All the operations were performed by the same surgical team, which had the experiences of more than 100 cases of laparoscopic and 100 cases of open radical gastrectomy with D2 lymph node dissection. The choice of surgical procedure was discussed by the surgeon and the patient, and decided according to the patient′s intension. Patients were divided into the laparoscopic group and open group according to the surgical method. Intraoperative and perioperative findings were compared between the two groups. The 3-year disease-free survival rate were analyzed with Kaplan-Meier survival curve and compared by using log-rank test. Results: A total of 37 consecutive patients were enrolled, including 21 in the laparoscopic group and 16 in the open group, and no one receiving laparoscopic procedure was converted to open surgery. The baseline data of two groups were comparable (all P>0.05). Compared with the open group, the laparoscopic group had significantly longer operation time [(264.0±35.1) minutes vs. (226.6±49.9) minutes, t=2.685, P=0.011], significantly less intraoperative blood loss [(65.7±37.4) ml vs. (182.2±94.6) ml, t=-4.658, P<0.001], significantly shorter time to postoperative flatus [(2.8±0.7) days vs. (4.1±0.7) days, t=-5.776, P<0.001] and significantly shorter postoperative hospital stay [(13.3±2.8) days vs. (16.6±4.3) days, t=-2.822, P=0.008]. Morbidity of postoperative complications, including anastomotic leakage, pancreatic fistula, abdominal abscess, intraperitoneal hemorrhage and duodenal stump leakage, in two groups was similar [19.0% (4/21) vs. 4/16, P=0.705]. There were no cases of anastomotic bleeding or stenosis. The 30-day postoperative mortality was 0 in the laparoscopic group and 1/16 in the open group, respectively (P=0.432). The 3-year disease-free survival rates were 38.1% and 37.5% in the laparoscopic and open group, respectively (P=0.751). Conclusion Laparoscopic total gastrectomy combined with distal pancreaticosplenectomy performed by experienced surgeons for T4b gastric cancer is safe and effective.