The aim of this study was to investigate the outcome of patients with muscle-invasive bladder cancer (MIBC) receiving neo-adjuvant chemotherapy (neo-CT) using a cisplatin-based regimen fractionated on days 1 and 8 of a 21-day cycle prior to organ-preservation (chemoradiation) or cystectomy. Patients with stage T2-T4, N0, M0, transitional cell carcinoma (TCC) of the bladder with a calculated glomerular filtration rate (GFR) ≥40 ml/min were eligible for inclusion in the study. Neo-CT comprised of gemcitabine (1,000 mg/m(2) d1, d8, q21) plus cisplatin (35 mg/m(2) d1, d8, q21) for four cycles. Following the administration of neo-CT, patients underwent surgery or radiotherapy (RT) with or without concurrent chemotherapy (CRT), based on the response to neo-CT and clinician and patient preference. A total of 23 patients were recruited: 21 males and 2 females; median age, 69 years (range, 49-85); stage T2=11, T3A=7, T3B=5, grade 2=1, grade 3=22. One patient progressed prior to neo-CT. In total, 75 cycles of neo-CT were administered. Treatment was well-tolerated with only one episode of neutropenic sepsis. Three of 22 patients developed early progression and did not receive radical treatment. For the remaining 19 patients, choice of definitive treatment (surgery vs. RT/CRT) was based on response to neo-CT. Eight patients had residual disease at cystoscopy following the completion of neo-CT; six patients underwent surgery and two underwent RT/CRT. A total of 11 patients had a complete response (CR) to neo-CT, nine of whom were treated by RT/CRT, with the remaining two declining radical treatment. Median follow-up for alive patients was 57 months (range, 4.4-68.5). Three-year survival was 37% (95% CI 17-58%) and 5-year survival was 31% (95% CI 15-52%). Neo-CT is effective and well-tolerated in MIBC. This split-dose cisplatin regimen facilitates treatment in an outpatient setting and allows inclusion of patients with compromised GFR.