Background: Bladder sparing trimodality therapy consisting of maximal TURBT, radiation, and chemotherapy offers a feasible and effective option to patients with muscle invasive bladder cancer that are unwilling to undergo cystectomy. The shape and position of the bladder change significantly during radiation therapy, and it is possible to miss the tumor bed when a radiation boost is delivered to only part of the bladder. This study describes the technique of injecting ethiodized oil in the submucosa of the urinary bladder wall as a novel modality to improve localization of muscle invasive bladder tumors prior to image-guided radiation therapy (IGRT). Methods: Eight patients underwent submucosal ethiodized oil injections at the time of transurethral bladder tumor re-resection. A rigid cystoscope with a working port was used to inject ethiodized oil into bladder submucosa circumferentially around the tumor bed (2-3 mm from margin of resection). Roughly 20-30 injections were used to demarcate the tumor bed for external beam radiation therapy, which was used as part of a bladder sparing approach. All patients were diagnosed with clinically localized, high-grade, muscle invasive carcinoma and were deemed nonsurgical candidates or were unwilling to undergo radical cystectomy. Results: 5 of the 8 patients underwent IGRT at our institution. 95% of ethiodized oil injections were visible on treatment planning CT scans and kV portal images throughout the 7-week course of IGRT. In 2 of 5 patients, the tumor bed based upon ethiodized oil extended outside a planning target volume that would have been treated with radiation therapy based upon cystoscopy reports and computed tomography scans without ethiodized oil. There were no adverse events or treatment-related toxicities secondary to ethiodized oil injection. Conclusions: Intravesical ethiodized oil injection is an easy-to-perform technique that is safe and effective. Ethiodized oil serves as a fiducial marker that improves tumor bed localization for radiation therapy, thereby reducing the likelihood of missing the tumor.