BACKGROUND AND PURPOSE: High BMI is a reason for medical inoperability in patients with endometrial cancer in the United States. Definitive radiation is an alternative therapy for these patients; however, data on patterns of failure after definitive radiotherapy are lacking. We describe the patterns of failure after definitive treatment with 3-D image-based high dose rate (HDR) brachytherapy for medically inoperable endometrial cancer. MATERIALS AND METHODS: Forty-three consecutive patients with endometrial cancer FIGO stages I-III were treated definitively with HDR brachytherapy with or without external beam radiation therapy. Cumulative incidence of failures was estimated and prognostic variables were identified RESULTS: Mean follow up was 29.7 months. Median BMI was 50.2 kg/m(2) (range: 25.1-104 kg/m(2)). The two-year overall survival was 65.2%. The two-year cumulative incidence of pelvic and distant failures was 8.3% and 13.5%, respectively. Grade 3 disease was associated with a higher risk of all-failures (Hazard Ratio [HR]: 4.67, 95% CI: 1.04-20.9, p=0.044). The incidence of acute Grade 3 GI/GU toxicities was 4.6%. CONCLUSIONS: Pelvic failure at two years was less than 10%. Patients with grade 3 disease were more likely to experience disease failure and may warrant closer follow up.