Background: Upper urinary tract urothelial carcinoma and muscle-invasive bladder cancer (MIBC) incidence rates are high in Taiwan. Our patients with MIBC are commonly managed with a radical cystectomy (RC); however, recurrence rates remain high. Aim: We aimed to establish a protocol regarding neoadjuvant chemotherapy (NAC) followed by RC or transurethral resection (TUR) alone from 2008 to 2013. We outline the efficacy and prognosis of NAC followed by RC. Methods: This was a retrospective study. The clinical data of 38 patients who underwent NAC from 2008 to 2013 at a single institution were retrospectively reviewed. Patients were divided into Group 1 (NAC with RC) and Group 2 (NAC with TUR alone). Age, sex, tumor size, prechemotherapy characteristics, and oncological outcomes were analyzed. Results: Group 1 had worse chemotherapy responses than Group 2 (48% vs. 71%, P = 0.0002). There were no significant differences in the 3-year progression-free survival and overall survival (OS) between the groups. High-risk patients were defined as having a tumor size ＞5 cm, concurrent hydronephrosis, and adverse pathological features. High-risk Group 1 patients had a better 3-year OS than high-risk Group 2 patients (13/17, 76%; and 3/5, 63%; respectively). Conclusion: In high-risk patients or patients with poor chemotherapy responses, NAC followed by RC with pelvic lymph node dissection resulted in a significantly increased 3-year OS. NAC with TUR alone was suitable only for low-risk patients with good chemotherapy responses.