Introduction and Objectives OSAKA regimen is a novel bladder preservation therapy involving balloon-occluded selective arterial infusion of radio-sensitizing chemotherapeutic agent with concurrent hemodialysis (HD), followed by radiation therapy. Objectives are to study the feasibility of this novel regimen in patients with advanced cancer bladder (Ca Bladder). Methods Two patients having advanced Ca Bladder with cisplatin ineligibility and poor performance status were managed with OSAKA regimen. Patients undergo super selective catheterisation of the anterior division of the internal iliac artery, followed by concurrent instillation of cisplatin (100 mg) via microcatheters and hemodialysis. Within 72 h, definitive radiation therapy is given. Image-guided radiation therapy (IGRT) with Helical Tomo using an Accuracy Radixact Tomography machine was used. 60 Gray/30 fractions is given to the bladder and nodes (50 Gray to bladder and nodes plus margin, with a boost of 10 Gray to bladder plus margin). Response is monitored by 3 monthly fluorodeoxyglucose positron emission tomography (FDG PET) imaging. Results Our first patient tolerated the procedure well and showed a complete response at 3 months of FDG PET imaging, but unfortunately, 1 year of FDG PET showed bony metastases, and the patient was managed accordingly. Our second patient also tolerated the regimen well, showed a complete response at 3 and 12 months of FDG PET imaging, and is under follow-up. Conclusions The OSAKA regimen, as a bladder preservation strategy, is feasible and safe in selective advanced Ca Bladder patients.