Standard treatment for transitional cell carcinoma confined to the bladder is radical cystectomy that allow to obtain an overall 5-year disease-free survival rate only of 50-70%. It has been demonstrated that intra-arterial chemotherapy produces the same survival outcomes as radical cystectomy. This study aimed to evaluate the activity and toxicity of a bladder-sparing loco-regional treatment. Five patients with transitional cell carcinoma of the bladder (4 locally advanced and 1 pelvic relapse) were treated with doxorubycin 25 mg/m2, cisplatin 40 mg/m2 and methotrexate 50 mg/m2, all infused bolus via internal iliac arteries on day 1, every three weeks. We obtained 3 complete responses, 1 stable disease and 1 progression of disease. The treatment was well tolerated with a minimal hematological toxicity and no others major toxicity. Median disease free survival was 8 months (1-17), median overall survival was 22 months (2-55). This loco-regional regimen of chemotherapy is active and safe in locally advanced bladder cancer patients and permits a prolonged good quality of life regarding the maintenance of the physiological functions of the lower urinary tract.