Definitive therapy for Stage I adenocarcinoma of the endometrium consists of total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pre- and/or post-operative radiotherapy (RT) is employed in selected patients with poor prognostic factors such as poorly differentiated tumors or deep myometrial invasion by tumor. The results are reported of RT alone in 69 patients with Stage I adenocarcinoma of the endometrium who presented with severe, acute, and chronic medical illnesses which prevented surgical management of their disease. Sixty-three patients (91.3%) were obese or hypertensive. Twenty-seven patients (39.1%) had diabetes mellitus, 16 (23.2%) had congestive heart failure, and the remaining patients had such conditions as stroke (17.4%), coronary artery disease (15.9%), and recent myocardial infarction (13.0%). The median age for this group of patients was 72.0 years compared to 60.0 years for a concurrent group of 304 patients with Stage I adenocarcinoma of the endometrium treated at our institution with combined surgery and RT. RT consisted of intracavitary insertions alone (11 patients), intracavitary plus low dose external beam therapy (9 patients), and intracavitary therapy plus high dose external beam therapy (49 patients, definitive RT). Younger patients and those with poorly differentiated disease were treated more aggressively. The 5- and 10-year overall survival for all patients was 76.8 and 33.3%, respectively. The 5- and 10-year disease-free survival was 88.1 and 82.4%, respectively. The 5-year overall and disease-free survival for the group of 49 patients treated with definitive RT was 85.4% and 88.7% with 15/49 (30.6%) having poorly differentiated tumors. For the definitive therapy group, the 5- and 10-year disease-free survival was 94.3, 92.3, and 78.0% for grades I, II, and III, respectively. Analysis of patterns of failure showed that none of the patients failed in the pelvis alone. Two out of 11 (18.2%) receiving intracavitary therapy alone and 3/49 (6.1%) receiving definitive RT failed in the pelvis with simultaneous distant metastasis (DM). Three patients in the definitive RT group failed with DM only. Severe complications occurred in 8 patients (16%), all of whom received definitive RT.