Objective: To investigate the difference in intra- and postoperative situations between totally laparoscopic and open radical gastrectomy, and the influential factors for complications. Methods: The clinical data of 330 gastric cancer patients undergoing radical gastrectomy from January 2014 to January 2017 were retrospectively analyzed. Of the patients, 150 cases underwent totally laparoscopic surgery (laparoscopic surgery group), and the other 180 cases underwent open surgery (open surgery group). The main clinical variables and complications were compared between the two groups of patients, and the influential factors for complications were analyzed. Results: The preoperative data were comparable between the two groups of patients. In laparoscopic surgery group compared with open surgery group, the operative time was prolonged, but the intraoperative blood loss, time for bowel function recovery and length of hospital stay were all significantly reduced (all P<0.05); the number of lymph node resection showed no significant difference (P>0.05). The overall incidence of postoperative complications in laparoscopic surgery group was significantly lower than that in open surgery group (8.67% vs. 32.22%, P<0.05), which was mainly responsible for the significantly reduced incidence of surgical complications such as intestinal obstruction, intra-abdominal hemorrhage, and incision infection (6.67% vs. 31.66%, P<0.05), but not for the incidence of non-surgical complications that showed no significant difference between the two groups (13.32% vs. 8.34%, P>0.05). Univariate analysis showed that age, BMI, operative time, preoperative levels of serum protein and hemoglobin, tumor size, lymph node metastasis and preoperative concomitant diseases were influential factors for the occurrence of complications (all P<0.05). Conclusion: Totally laparoscopic radical gastrectomy has the advantages of minor trauma and quick postoperative recovery, and also has better control of the overall complications than open surgery. So it is recommended to be used in clinical practice.