292 Background: Though Level I evidence supports the use of neoadjuvant chemotherapy (NAC) in BCa, the data supporting AC has been mixed. Experience suggests an adequately powered trial to definitively assess the role of AC is unlikely to be completed. Alternative approaches to evidence development are necessary. Methods: Patients who underwent cystectomy for ≥pT3 and/or pN+ M0 BCa were identified from the National Cancer Database. Patients who received NAC and/or diagnosed after 2006 (most recent year with survival data) were excluded. Logistic regression was used to calculate propensity scores representing the predicted probabilities of assignment to AC versus observation based on: age, demographics, year of diagnosis, pT stage, margin status, lymph node density, distance to hospital, hospital cystectomy volume, and hospital type and location. A propensity score-matched cohort of AC versus observation (1:2) patients was created. Stratified Cox proportional hazards regression was used to estimate the hazard ratio (HR) for overall survival for the matched sample while propensity score adjusted and inverse probability of treatment weighted proportional hazards models were used to estimate adjusted HR for the full sample. A sensitivity analysis examined the impact of comorbidities. Results: 3,294 patients undergoing cystectomy alone and 937 patients undergoing cystectomy plus AC met inclusion criteria.Patients receiving AC were significantly more likely to: be younger, have more lymph nodes examined and involved, have higher pT stage, have positive margins, reside in the Northeast and closer to the hospital, and have private insurance. AC was associated with improved overall survival (Table). The results were robust to sensitivity analysis for comorbidities. Conclusions: AC was associated with improved survival in patients with ≥pT3 and/or pN+ BCa in this large comparative effectiveness analysis. [Table: see text]