<h3>Purpose/Objective(s)</h3> Endometrial cancer (EC) is the most common gynecologic malignancy in the U.S. Brachytherapy alone or in combination with external beam radiation therapy (EBRT) is considered an alternative definitive treatment for women who are not surgical candidates, though limited data exists for outcomes with modern 3D image-guided brachytherapy. As the U.S. population ages and rates of obesity and other comorbidities rise, more women may require definitive radiation therapy. In this study, we report outcomes for a large cohort of patients treated with intrauterine brachytherapy with 3D CT-guided planning. <h3>Materials/Methods</h3> Retrospective review identified 59 women with EC who received high dose rate (HDR) intrauterine brachytherapy with dual or triple tandem applicators with definitive intent, alone or in combination with EBRT, between 2009-2020. All patients underwent endometrial biopsy and 92% had pretreatment diagnostic CT and/or MRI imaging. 3D CT-guided brachytherapy planning was done using planning software. Local failure-free survival (LFFS), disease-free (DFS), and overall survival (OS) estimates were calculated by Kaplan-Meier method. Median follow-up was 44 months (interquartile range [IQR], 17-88). <h3>Results</h3> Median patient age was 68 years (range, 37-87). Patients had atypical complex hyperplasia (15%), or clinical stage I (76%), II (5%), or III (3%) EC. Patients were ineligible for surgery due to medical comorbidities, including obesity (97% of patients), pulmonary disease (36%), cardiovascular disease (41%), renal disease (9%), or complicated prior surgical history (9%). Median BMI was 45.7 kg/m<sup>2</sup> (range, 17.2-79.7), and 64% of patients met criteria for severe obesity (≥40 kg/m<sup>2</sup>). Brachytherapy dose delivered ranged from 8.5Gy in 1 fraction to 36.5Gy in 5 fractions. Among patients receiving brachytherapy alone, 83% were treated with 34Gy in 4 fractions. 20% of patients underwent EBRT immediately prior to or following brachytherapy and received lower doses of brachytherapy. Median coverage of the uterus CTV V100 = 92% (range, 65%-99%). 5-year LFFS, DFS, and OS rates were 91%, 82%, and 75%, respectively. Median time to any failure was 15 months (IQR, 10-26). Among 59 patients, 4 failed locally, 3 failed in the peritoneum, and 2 failed both locoregionally and distally. Two of 4 patients who failed locally were successfully salvaged with surgery. Five patients died of EC. Ten patients (17%) had perforation of the uterus with applicator placement. Antibiotics were not given prophylactically and no patients developed bacterial peritonitis or other infectious complication. There was no correlation between perforation of the uterus at the time of brachytherapy and peritoneal spread of EC. <h3>Conclusion</h3> Outcomes following definitive 3D image-guided brachytherapy were excellent, with 5-year LFFS of 91% and 5-year DFS of 82%. Patients rarely died of EC. Our data supports the use of 3D brachytherapy as definitive therapy for patients who are not candidates for surgery.