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The current guidelines do not recommend adjuvant chemotherapy (AC) for patients with adverse pathologic findings after neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for bladder cancer. We sought to evaluate the association of AC with overall survival (OS) in these patients.The National Cancer Database was used to identify patients with adverse pathologic findings (ypT3N0, ypT4N0, or ypTanyN1-N3) after NAC and RC for bladder cancer from 2006 to 2012. The clinicopathologic variables were abstracted, and the patients were stratified according to the receipt of AC. OS was estimated using the Kaplan-Meier method and log-rank test. Associations between AC and OS were evaluated in multivariable Cox proportional hazards regression models among all patients and stratified by pathologic classification.A total of 1361 patients were identified: 444 (32.6%) with ypT3N0, 162 (11.9%) with ypT4N0, and 755 (55.5%) with ypTanyN1-N3. The median OS for the entire cohort was 22.9 months, which differed by pathologic classification: 34.6 months with ypT3N0, 21.4 months with ypT4N0, and 19.3 months with ypTanyN1-N3 (P < .01). AC was used in 328 patients (24.1%), and no difference in OS was observed by receipt of AC (24.6 months with AC vs. 22.0 months without; P = .18). On multivariable analysis, AC was not independently associated with OS (hazard ratio, 0.86; 95% confidence interval, 0.74-1.01; P = .06).Patients with adverse pathologic findings at RC after previous NAC have a median OS of approximately 2 years, which was not significantly improved with AC. Clinical trials with newer systemic agents are warranted for patients in this setting to guide future therapy.Few data are available to guide therapy for patients with adverse pathologic findings (ypT3/T4 or ypN+) after neoadjuvant chemotherapy and radical cystectomy for bladder cancer. We reviewed the National Cancer Database to evaluate the association of adjuvant chemotherapy with overall survival in these patients. Adjuvant chemotherapy was not significantly associated with differences in overall survival (24.6 months vs. 22.0 months) after radical cystectomy and neoadjuvant chemotherapy. The current data are insufficient to support the use of adjuvant chemotherapy in this setting outside of a clinical trial.