Objective: To identify the risk factors of perioperative complications after radical gastrectomy for gastric cancer. Methods: A retrospective case-control study was performed. Case inclusion criteria: (1) patients undergoing radical gastrectomy (D2); (2) primary gastric cancer without distant organ metastasis confirmed by postoperative pathology; (3) no neoadjuvant chemotherapy before surgery. Patients with peritoneal tumor dissemination found during operation, undergoing palliative operation due to distant metastasis, and undergoing combined organ resection and those without complete clinicopathological data were excluded. According to the above criteria, 426 patients with gastric cancer at our department from January 2015 to June 2017 were included in this study. Of 426 patients, 285 were male and 141 were female with a mean age of (55.4±9.7) years. According to the "Japan Clinical Cancer Research Group (JCOG) classification criteria for postoperative complications of gastric cancer", patients with grade II and higher complications were classified as complication group, and patients with no complication or grade I complication were classified as non-complication group. Baseline data were compared between two groups. Associations of perioperative complication with gender, age, body mass index, preoperative routine laboratory test, American Society of Anesthesiologists (ASA) classification, activities of daily living (ADL) assessment, past medical history as well as preoperative conditions (hypertension and/or diabetes), surgical resection procedure, incision type, operation time, intraoperative blood loss/body mass ratio were examined. Univariate analysis was performed using χ² test and the Wilcoxon rank sum test to screen the statistically significant variables associated with perioperative complications. The significant variables were included in multivariate logistic regression analysis to identify risk factors of perioperative complication. Results: Grade II or higher complications after surgery were developed in 97 patients (22.8%), which included anastomotic leakage in 18 cases (4.2%), postoperative bleeding in 9 cases (2.1%), abdominal abscess in 5 cases (1.2%), intestinal obstruction in 5 cases (1.2%), pancreatic leakage in 1 case (0.2%), and other adverse events in 59 cases (13.8%). Univariate analysis suggested that the gender, age, ADL, incision type, intraoperative blood loss/body mass ratio, and operation time were associated with perioperative complication (all P<0.05). Multivariate analysis revealed that elder age (OR=1.033, 95% CI:1.013-1.053, P=0.013), incision type of laparotomy (OR=2.091, 95% CI:1.247-3.508, P=0.004), longer operation time (OR=1.004, 95% CI:1.001-1.007, P=0.001) and higher ratio of intraoperative blood loss/body mass (OR=1.100, 95% CI: 1.039-1.163, P=0.031) were risk factors for postoperative complications. Conclusion Attention should be paid to those cases with elder age, laparotomy incision, longer operation time and higher ratio of intraoperative blood loss/body mass, and perioperative management after gastrectomy should be improved.