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Surgical site infection (SSI) is 1 of the frequent postoperative complications after colorectal cancer surgery. Oral health care has been reported to reduce the risk of SSI or postoperative pneumonia in oral, esophageal, and lung cancer surgeries. The purpose of the study was to investigate the preventive effect of perioperative oral management on the development of SSI after a major colorectal cancer surgery.The medical records of 698 patients who underwent colorectal cancer surgery at 2 hospitals in Japan were reviewed. Among these patients, 563 patients received perioperative oral management (oral management group) and 135 did not (control group). Various demographic, cancer-related, and treatment-related variables including perioperative oral management intervention and the occurrence of SSI were investigated. The relationship between each variable and the occurrence of SSI was examined via univariate and multivariate analyses using Fisher exact test, 1-way analysis of variance (ANOVA), and logistic regression. The occurrence of SSI in the 2 groups was evaluated via logistic regression using propensity score as a covariate. The difference in mean postoperative hospital stay between the oral management and control groups was analyzed using Student's t test.SSI occurred in 68 (9.7%) of the 698 patients. Multivariate analysis showed that operation time, blood loss, and perioperative oral management were significantly correlated with the development of SSI. However, after the propensity score analysis, not receiving perioperative oral management also became a significant risk factor for SSI. The odds ratio of the oral management group was 0.484 (P = .014; 95% confidence interval: 0.272–0.862). Mean postoperative hospital stay was significantly shorter in the oral management group than in the control group.Perioperative oral management reduces the risk of SSI after colorectal cancer surgery and shortens postoperative hospital stay.