Introduction To describe the technique of injecting Lipiodol in the submucosa of the urinary bladder wall as a novel modality to improve localization of muscle-invasive bladder tumors before image-guided radiation therapy. Technical Considerations Eight patients underwent submucosal Lipiodol injections at transurethral bladder tumor reresection. A rigid cystoscope with a working port was used to inject Lipiodol into bladder submucosa circumferentially around the tumor bed (2-3 mm from margin of resection). Approximately 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. Five of the 8 patients received radiation at our institution. Lipiodol injections (95%) were visible on treatment planning computed tomographic scans and kilovoltage portal images throughout the 7-week course of image-guided radiation therapy. In 2 of 5 patients, the tumor bed based on Lipiodol extended outside a planning target volume that would have been treated with radiation therapy based on cystoscopy reports and computed tomographic scans without Lipiodol. There were no adverse events or treatment-related toxicities secondary to Lipiodol injection. Conclusion Intravesical Lipiodol injection is an easy-to-perform technique that is safe and effective. Lipiodol serves as a fiducial marker that improves tumor bed localization for radiation therapy, thereby reducing the likelihood of missing the tumor. © 2014 Elsevier Inc. All Rights Reserved.