BACKGROUND: Radiomicrosphere therapy (RT) utilizing yttrium-90 (90Y) microspheres has been shown to be an effective regional treatment for primary and secondary hepatic malignancies. We sought to determine a large academic institution's experience regarding the extent and frequency of gastrointestinal complications. METHODS: Between 2004 and 2007, 27 patients underwent RT for primary or secondary hepatic malignancies. Charts were subsequently reviewed to determine the incidence and severity of GI ulceration. RESULTS: Three patients presented with gastrointestinal bleeding and underwent upper endoscopy. Review of the pretreatment angiograms showed normal vascular anatomy in one patient, sclerosed hepatic vasculature in a patient who had undergone prior chemoembolization in a second, and an aberrant left hepatic artery in a third. None had undergone prophylactic gastroduodenal artery embolization. Endoscopic findings included erythema, mucosal erosions, and large gastric ulcers. Microspheres were visible on endoscopic biopsy. In two patients, gastric ulcers were persistent at the time of repeat endoscopy 1-4 months later despite proton pump inhibitor therapy. One elderly patient who refused surgical intervention died from recurrent hemorrhage. CONCLUSION: Gastrointestinal ulceration is a known yet rarely reported complication of 90Y microsphere embolization with potentially life-threatening consequences. Once diagnosed, refractory ulcers should be considered for aggressive surgical management.