Background: Neoadjuvant chemotherapy followed by cystectomy in MIBC is associated with improved survival compared to cystectomy alone. Recent retrospective studies indicated that secondary MIBC (non-MIBC progressed to MIBC) had worse outcome with cisplatin based neoadjuvant chemotherapy when compared to primary MIBC. To further evaluate this observation, we queried our database to assess the differential response and determine if prior use of intravesical therapy diminishes the effect of cisplatin based neoadjuvant chemotherapy. Methods: A total of 387 patients diagnosed with T_2-4 or N_0-3 and M₀ from 2000-2018 and underwent cystectomy were retrospectively chart reviewed for demographics, treatment and outcomes at University of Iowa Holden Comprehensive Cancer Center. Cox regression models were utilized to assess differences in recurrence-free survival (RFS) and overall survival (OS). Time was calculated from cystectomy to recurrence or death due to any cause for RFS and OS, respectively. Results: Of the 387 patients, 324 patients had primary MIBC and 63 had secondary MIBC. Median follow up was 25.8 months. Intravesical therapy was administered to 98% (62/63) of secondary MIBC patients. Neoadjuvant chemotherapy was administered to 38% (122/324) of primary MIBC patients and 21% (13/63) of secondary MIBC patients. NAC had no difference in response rates (CR and PR) for primary vs secondary MIBC (p=0.73). Additionally, there was no difference between the primary and secondary MIBC with regards to RFS (p=0.54) and OS (p=0.12) on univariate analysis. The effect of neoadjuvant chemotherapy did not differ based on prior use of intravesical therapy in terms of RFS (p=0.61) or OS (p=0.40). Additionally, neoadjuvant chemotherapy irrespective of prior use of intravesical therapy was not associated with RFS (p=0.66) or OS (p=0.15). Conclusions: Prior intravesical therapy was not associated with differential efficacy of neoadjuvant chemotherapy in secondary MIBC when compared to primary MIBC.