Patients with node-positive (LN+) uterine or cervical cancer often require adjuvant radiation to the pelvis and para-aortics, resulting in significant acute and late gastrointestinal (GI) and genitourinary (GU) toxicity. Proton therapy allows for more conformal delivery of radiation dose. The objective was to prospectively evaluate the safety and efficacy of proton beam radiation therapy (RT) for patients with LN+ uterine or cervical cancer requiring RT.Patients with IIIC uterine and pT1,2N1M0 cervical cancer status post hysterectomy and lymphadenectomy were eligible. Sequential (uterine) and concurrent (cervical) chemotherapy were allowed. Exclusion criteria included life expectancy < 18 months, residual/measurable disease and prior RT. Treatment plans for proton pencil beam scanning were generated. Pelvic RT (PRT) extended to L5-S1. Extended field RT (EFRT) extended to T12-L1. Patients received 45 Gy (RBE) in 25 fractions, followed by vaginal brachytherapy (VB) to 15 Gy in 3 fractions to surface. Patients were followed with exam and imaging per protocol through 5 years. The primary endpoint was comparison of dose volume histogram (DVH) of PBS vs IMRT and 3DCRT which will be reported at a later date. Secondary endpoints include progression free survival (PFS), overall survival (OS), toxicity (CTCAE v4.02), patterns of recurrence, and quality of life (QOL using FACT-En/Cx V4). PFS and OS were analyzed using the Kaplan-Meier method and defined as from the start of protocol treatment to time of disease progression or death. Patients who did not progress or die were censored at time of last follow up. Data reporting was allowed once all patients completed 2 yrs follow up with the exception of late toxicity and QOL which will be presented after 5 yrs.21 patients completed RT between 10/2013 and 10/2018. Median follow-up is 52.3 months (range, 11.2-63.4). Median age was 59.7 years (range, 31.5-79.2). 15 patients had IIIC uterine cancer (13 endometrioid) and 6 patients had cervical cancer. 52% received sequential and 29% received concurrent chemotherapy. Median dose was 45.0 Gy (RBE). 20 (95%) received VB boost. 4 received PRT and 17 EFRT. Acute grade 2 and 3 GI toxicity was 24% and 14%, respectively. Acute grade 2 and 3 GU toxicity was 10% and 0%, respectively. Acute grade 2 and 3 hematologic toxicity was 24% and 0%, respectively. To date, there have been no late toxicities > grade 3. The 2-year PFS was 81% (95% CI, 56%-92%). Of the 5 patients that recurred, 4 were peritoneal and 1 was abdominal wall and lung; no recurrences were in-field. The 2-year OS was 86% (95% CI, 62%-95%).Scanned proton beam RT appears effective in preventing local-regional recurrence in LN+ patients with uterine and cervical cancer undergoing adjuvant radiation. Acute toxicity is low and severe late effects have not been observed but await longer follow-up.A.L. Russo: None. K.D. Bernstein: None. S.P. Nisbet: None. N. Horick: None. N. Depauw: None. B.Y. Yeap: None. H.M. Kooy: None. T.F. DeLaney: None. A.H. Russell: None.