Purpose: To evaluate the outcomes of patients with localized muscle invasive bladder cancer (MIBC) treated with neo-adjuvant chemotherapy followed by continuous chemo-radiation (cCRT). To evaluate the prognostic significance of clinical complete response to neo-adjuvant chemotherapy in the setting of bladder preservation. Materials/Methods: From 2002 to 2012, twenty-two patients with cT2-4 N0-2 M0 MIBC were treated using cCRT for bladder preservation. All patients were felt to be medically inoperable and/or refused cystectomy. They were treated with maximal transurethral tumor resection (TURBT) and multiple cycles of platinum-doublet-based neoadjuvant chemotherapy, followed by definitive cCRT. Tumor response was evaluated with an abdomino-pelvic CT scan and cystoscopy 4 weeks after neoadjuvant chemotherapy and 3 months after completion of all therapy. Radiation therapy was delivered using 3DCRT or IMRT to a median dose of 45 Gy to the pelvis and 63 Gy to the bladder (range 41.4 Gy to 71.4 Gy). Three-year local control (LC) and disease-free survival (DFS) estimates were determined by the Kaplan-Meier method and log rank analysis. Results: The median age was 67.5 years. Median follow-up was 24 months (range 6 to 86). Clinical stage was T2 in 12 patients, T3 in 8, and T4 in 2. Fourteen patients were node-negative while 8 were node-positive. Actuarial 3-year OS, DFS, LC for the entire cohort were 62.2%, 62% and 78.3%, respectively. Furthermore, the 3-year OS and DFS for patients achieving a CR on cystoscopy following neo-adjuvant chemotherapy was 64.6% vs. 57.1% without CR (p=.046), and 64.3% vs. 57.1% without CR (p=.03). The 3-year LC was 90.9% in patients showing complete response to neo-adjuvant chemotherapy. When stratified by T stage, 3-year LC was 90.9% for T2, 87.5% for T3 and 0% for T4 (p=.007). Local failure was associated with distant metastases in 4 out of 5 patients. Two patients had non-invasive local recurrences and both were successfully treated with intra-vesical BCG. Conclusions: Maximal TURBT followed by neo-adjuvant platinum based chemotherapy and definitive cCRT offers good rates of OS, DFS and LC in MIBC at three-years of follow-up. Complete response to neo-adjuvant chemotherapy is a favorable prognostic factor, achieving LC rates >90% at 3 years.