AbstractPurposeTo clarify the necessity and effect of a single intraoperative instillation of chemotherapy during radical cystectomy.MethodsPatients who underwent radical cystectomy for bladder cancer between January 2013 and April 2019 were retrospectively evaluated and divided into a non‐instillation group and an instillation group according to the intraoperative instillation of chemotherapy. Univariate and multivariate Cox regression was used to determine the clinical predictors of overall survival and disease‐free survival. Kaplan–Meier analysis and log‐rank tests were performed to analyze overall survival and disease‐free survival.ResultsOf the 320 patients who were enrolled in the study, 113 underwent radical cystectomy with intraoperative instillation of chemotherapy. Univariate Cox analysis showed that intraoperative instillation was not a risk factor for overall survival or disease‐free survival (HR: 1.04, 95% CI: 0.66–1.63,p= 0.864; HR: 1.11, 95% CI: 0.76–1.62,p= 0.602, respectively). As shown in the Kaplan–Meier analysis, no significant differences were noted in overall survival (p= 0.857) and disease‐free survival (p= 0.600) between the two groups. A subgroup analysis demonstrated that intraoperative instillation was not associated with a statistically better overall survival and disease‐free survival in the nonmuscle invasive (p= 0.852 and 0.836) and muscle‐invasive (p= 0.929 and 0.805) patients.ConclusionA single intraoperative instillation of chemotherapy during radical cystectomy was not related to better disease‐free survival or overall survival. It is unnecessary to consider single instillation of chemotherapy as a regular procedure during radical cystectomy.