Prospective trials in early stage endometrial cancer demonstrate increased locoregional control with adjuvant radiotherapy for patients with high risk features. VCB is widely utilized, yet there is substantial practice variation and limited randomized data examining optimal dose/fractionation. We aimed to study the safety and efficacy of short course VCB compared to commonly used regimens. We conducted a prospective, randomized, multicenter trial examining short course adjuvant VCB (11 Gy x 2 fractions at the surface) compared with other standard regimens (7 Gy x 3 fractions at 0.5 cm depth, 6 Gy x 5 fractions at the surface, or 5-5.5 Gy x 4 fractions at 0.5 cm depth). Eligible patients underwent hysterectomy and had pathologically confirmed endometrioid adenocarcinoma, serous, clear cell, or carcinosarcoma. Patients with stage I and II cancers were included, with lymphovascular invasion (LVI) required for stage IAG1. The primary outcome was Global Health Status measured by the EORTC QLQ-C30 with a pre-specified non-inferiority margin of 15 points. Secondary outcomes included patient-reported outcomes, toxicities as assessed by CTCAEv5, and patterns of recurrence. Data were collected at each brachytherapy fraction and at 1-, 6-, and 12-month follow-up. One hundred eight patients were enrolled, 54 in each study arm. Data completion was 94%, 91%, and 77% at 1 month, 6 months, and 12 months, respectively. 70% of patients had endometrioid adenocarcinoma, 18% serous carcinoma, and 12% other histologies. 23% were FIGO grade 1, 33% grade 2, and 43% grade 3 or high risk histologies. The majority of patients were stage I (56% IA, 38% IB). 22% of patients had LVI. The QLQ-C30 Global Health Status for the experimental arm was within the predefined boundary and thus 2 fractions were non-inferior to standard of care at one month (p = 0.000005) and 12 months (p = 0.0005). Using EORTC EN24 for patient reported vaginal/sexual, urologic, and gastrointestinal symptoms, the change in mean patient reported symptom score from baseline to 1 month and baseline to 12 months were not significantly different between arms. Using CTCAEv5, 51 patients experienced short-term AEs related to study treatment, 20 in the experimental arm and 31 in the control arm (p = 0.053). All study treatment-related AEs were grade 1-2, except for two grade 3-4 AEs, both on the control arm. At median follow-up of 19 months, the isolated vaginal control rate in each arm was 100%. There was no significant difference in the total number of recurrences between study arms, with 3 distant and 3 distant/pelvic/vaginal recurrences in the experimental arm, and 2 distant, 2 pelvic, and 1 pelvic/vaginal recurrence in the control arm. Short course VCB is safe with acceptable acute toxicity and non-inferior patient reported outcomes. Short course VCB improves patient convenience and may improve access to care for rural or underserved populations while providing similar local control.