Abstract This is a single arm prospective phase II study conducted to assess the efficacy of fractionated weekly cisplatin-based neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC) who are unfit for the standard 21-days chemotherapy regimen due to impaired renal function. Twenty-five patients were recruited between February 2015 and July 2017. Inclusion criteria were; age ≥18 years old, histopathologically-proven urothelial bladder cancer, stage T2-T4a, calculated glomerular filtration rate (GFR) of 40-60 ml/min, no metastasis and with adequate organ function. Chemotherapy given was cisplatin (35 mg/m2 d1, d8, and q21) plus gemcitabine (1,000 mg/m2 d1, d8, and q21) for three cycles followed by local therapy. Median age was 63 years (Mean±SD; 60.76 ±1.67 years). Most patients (21/25; 84%) were males. Almost half of the patients (13/25; 52%) had T3.Treatment was well-tolerated. All patients completed the scheduled 3 Cycles. 3 (12%) patients developed complete response, 10 (40%) partial response, 6 (24%) stable disease, while 6 (24%) developed progression. Median survival was 23 months (95% CI; 18.1-27.89). Fifteen (60%) patients underwent surgery, while 5 (20%) patients underwent bladder preservation. Four (16%) patients were shifted to palliative care and 1(4%) patient declined any further treatment. In conclusion, fractionated weekly cispaltin-gemcitabine neoadjuvant chemotherapy in MIBC patients with impaired renal function is feasible and safe with good clinical response. Further larger studies are warranted.