Background: Efficacy of cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) for T2-4aN1M0 muscle-invasive bladder cancer (MIBC) was proved by randomize controlled trials. Recent retrospective studies suggested that MIBC patients who had a history of non-muscle invasive bladder cancer (NMIBC) had lower pathologic complete response and worse overall survival rate to NAC and RC. This study aimed to compare clinical outcomes between MIBC that progressed from NMIBC (secondary MIBC) and primary MIBC. Methods: A retrospective analysis of patients with urothelial carcinoma (cT2-4aN0-1M0) who received neoadjuvant chemotherapy from January 2011 and December 2017 in Asan Medical Center was conducted. Clinicopathologic outcomes were compared between 187 patients with primary MIBC and 38 patients with secondary MIBC. Results: Baseline characteristics are well balanced between the groups. Downstaging rate ( < ypT2 and no N upstaging) are 46.7% for secondary MIBC group, 55.6% for primary MIBC group (p = 0.390), and positive pathologic metastatic nodes (ypN1+) are observed in 23.3% for secondary MIBC group, 18.3% for primary MIBC group (p = 0.523). There were no differences in overall survival (OS) (3 year OS 69.3% for secondary MIBC, 70.3% for primary MIBC, p = 0.420), disease-free survival (DFS) (3 year DFS 57.7% vs 56.6%, p = 0.880) between the groups. History of NMIBC is not independent prognostic factor for OS on multivariable analysis. Conclusions: Patients with secondary MIBC treated with NAC showed no differences in NAC response, pathologic downstaging rate, OS, DFS compared to patients with primary MIBC. Prospective or larger cohort study are required in the future. Genomic analysis is ongoing to identify genetic differences between two groups.