Painful splenomegaly has a clinical presentation that is often associated with myeloproliferative disorders, such as acute or chronic lymphoblastic or myelogenous leukemia. In these situations low-dose radiotherapy is effective in reducing the splenomegaly and relieving pain. The potential benefit of radiotherapy for cardiogenic splenomegaly is less well established. The present report discusses a case in which radiotherapy was employed to benefit a patient with Eisenmenger's-associated painful splenomegaly. Because of the patient's high anesthesia risk, palliative surgical splenectomy was not feasible. The patient underwent three-dimensional conformal treatment planning, and a total of 42.5 Gy at 2.5 Gy per fraction was prescribed to the spleen. At 4 months following radiotherapy completion, the patient reported durable pain relief and no untoward small bowel effects; moreover, there was a 43% reduction in splenic volume on follow-up CT. Although there have been previous reports of hematological and myeloproliferative-associated splenomegaly that have been treated with a lower dose per fraction and lower total dose radiotherapy, we advocate the use of 2.0-2.5 Gy per fraction to a total dose approaching 40 Gy for adequate duration of response when treating cardiogenic-associated painful splenomegaly in patients for whom surgical splenectomy cannot be performed.