The optimal adjuvant management of FIGO Stage III endometrial cancer (EC) remains a source of debate. Initial data from GOG-258 demonstrate that treatment with radiation therapy (RT) prior to chemotherapy (CT) yields a sizable benefit in locoregional control, but is not associated with a survival benefit compared to CT alone. Additionally, treatment with RT prior to CT may be associated with a higher risk of distant metastatic disease, suggesting a detriment to CT delay. The aim of this study was to assess the optimal selection and sequencing of adjuvant therapies in this population. The 2004-2014 National Cancer Database was queried for women with FIGO Stage III EC who underwent hysterectomy Women who received single-agent CT only or <45Gy of regional RT were excluded. Sequence of RT and CT was determined by documented treatment start date(s). To account for immortal-time bias, women with <12 months of follow-up were excluded. A series of observational matched cohort analyses were performed using propensity score-matched cohorts. Additional separate matched cohort analyses were performed for women with Type I (Grade 1/2 endometrioid) and Type II (Grade 3/4 endometrioid, serous, carcinosarcoma, clear cell, and mixed histologies) EC. Kaplan-Meier and multivariable accelerated failure time (AFT) survival analyses were used to calculate absolute and relative survival estimates. Of the 22,197 women identified, 34.1% (n=7,568) received RT after CT, 9.7% (n=2,165) received RT before CT, 41.1% (n=9,134) received CT alone, and 15.0% (n=3,330) received RT alone. Matched cohorts were well balanced for all clinical variables. Treatment with RT after CT was associated with significantly longer OS compared to treatment with RT before CT (5-year OS: 68.9% versus 64.5%; TR=1.10, 95% CI=1.06-1.15, P<0.001), as well as compared to CT alone (5-year OS: 65.6% versus 56.1%; TR=1.22, 95% CI=1.19-1.26), or RT alone (5-year OS: 67.6% versus 59.6%; TR=1.19, 95% CI=1.14-1.24, P<0.001). This survival benefit was also seen in the subset analyses of women with Type I EC (5-year OS: 82.5% versus 77.8%; TR= 1.17, 95% CI=1.08-1.26, P<0.001), as well as Type II EC (5-year OS: 58.9% versus 54.4%; TR= 1.06, 95% CI=1.02-1.09). Accounting for known prognostic factors, women who received CT as the first adjuvant therapy followed by RT experienced significantly longer OS than women who received RT prior to CT or either therapy alone. For women with FIGO stage III endometrial cancer, treatment with CT followed by volume-directed RT (or a sandwich approach) may be the optimal adjuvant multimodality regimen. These data support the inclusion of a CT followed by RT arm in future prospective trials and suggest that RT maintains an important role in the treatment of stage III endometrial cancer.