Background: Whole pelvic radiation therapy (WPRT) improves locoregional control in women with high-intermediate and high-risk endometrial cancer. The standard treatment course consists of 25-28 fractions (5-5.5 weeks) of 1.8-2 Gy/fraction, and is delivered using intensity-modulated radiation therapy (IMRT), which allows for superior sparing of normal tissue with a subsequent lower rate of acute and late toxicity compared to less conformal treatment techniques. Moderate hypofractionation (HF, >2 Gy/fraction) has been studied in other disease sites, such as breast and prostate cancer, and is associated with lower or comparable toxicity, improved patient convenience, and greater cost savings compared to standard fractionation. However, HF has not been well-studied in the setting of WPRT for gynecologic cancers. Methods: This phase I/II multi-institutional study evaluates the feasibility, safety, and toxicity profile of HF-WPRT in women with non-metastatic cervical or endometrial cancers who have undergone curative hysterectomy and are recommended adjuvant WPRT by their treating physician. Concurrent chemotherapy is not allowed, but can be administered sequentially prior to or after WPRT. Para-aortic radiation or nodal boosts are not allowed, however vaginal brachytherapy boost is permissible. Phase I is a safety study of increasing dose-per-fraction. All treatment regimens have an approximate biologic effective dose of 53 Gy (α/β =10). A keyboard design is utilized to identify the maximum tolerated dose-per-fraction (MTD), defined in this study as the regimen that is associated with a CTCAE grade 3+ gastrointestinal/genitourinary toxicity rate of ≤10% on the last day of WPRT. There are 3 dose cohorts of increasing dose-per-fraction. Phase II will accrue 64 evaluable patients to HF-WPRT using the MTD determined in phase I. The primary endpoint is to evaluate the change in patient-reported gastrointestinal toxicity from baseline to the last day of WPRT using the EPIC bowel score. The study is powered to compare results to the RTOG 1203 IMRT standard fractionation arm. The phase 1 portion of the study completed accrual; the phase II portion opened in April 2022 with a fractionation of 42.56 Gy in 16 fractions. Secondary endpoints include genitourinary toxicity (EPIC, CTCAE), quality of life (FACT-Cx, PRO-CTCAE), financial toxicity (FACIT-COST), and decision-making (Decision Regret Scale). Pelvic control at 2 years is an exploratory endpoint. Clinical trial information: NCT04683653.