Abstract: OBJECTIVE To compare the incidence of surgical site infection (SSI) between natural orifice specimen extraction surgery (NOSES) and conventional laparoscopic radical resection for rectal cancer and analyze the risk factors for SSI in the patients undergoing the radical resection for rectal cancer. METHODS The clinical data were collected from 3 114 patients who underwent the radical resection for rectal cancer in the Cancer Hospital of Chinese Academy of Medical Sciences from Jan. 2015 to Dec. 2019 and were analyzed by means of retrospective cohort study combined with propensity score matching method. The patients were divided into the NOSES group with 383 cases and the conventional laparoscopy group with 2731 cases. The patients were matched in a 1∶1 ratio based on preoperative data (with a matching coefficient of 0.05), 367 patients were included in each group after being matched, and the baseline was balanced. The short-term postoperative complications were compared between the two groups, and univariate analysis and multivariate logistic analysis were performed for the risk factors for SSI. RESULTS The incidence of postoperative SSI of the NOSES group was 2.45% after PSM, lower than 3.00% of the conventional laparoscopy group; the incidence of anastomotic fistula of the NOSES group was 1.09%, lower than 2.18% of the conventional laparoscopy group; there were no significant differences. Univariate analysis showed that male (P=0.039), stomal leak and perioperative hemorrhage no less than 400 ml( all P＜0.001) were associated with the SSI. Multivariate analysis indicated that the perioperative hemorrhage no less than 400 ml(OR=2.193,P=0.015)and anastomotic fistula(OR=84.468,P＜0.001) were the risk factors for the postoperative SSI in the patients undergoing radical resection for rectal cancer. CONCLUSIONS The incidence rates of postoperative SSI and anastomotic fistula are lower in the patients undergoing NOSES than in the patients undergoing the conventional laparoscopy, but there are no significant differences. The perioperative hemorrhage no less than 400 ml and anastomotic fistula are the risk factors for the postoperative SSI in the patients undergoing radical resection for rectal cancer.