BACKGROUND Stage III or IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence. METHODS In this randomized phase 3 trial, we tested whether 6 months of platinumbased chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapsefree survival (primary end point) than six cycles of combination chemotherapy alone in patients with stage III or IVA endometrial carcinoma. Secondary end points included overall survival, acute and chronic toxic effects, and quality of life. RESULTS Of the 813 patients enrolled, 736 were eligible and were included in the analysis of relapsefree survival; of those patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy and 361 received chemotherapy only). The median followup period was 47 months. At 60 months, the Kaplan–Meier estimate of the percentage of patients alive and relapsefree was 59% (95% confidence interval [CI], 53 to 65) in the chemoradiotherapy group and 58% (95% CI, 53 to 64) in the chemotherapyonly group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with a lower 5year incidence of vaginal recurrence (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and pelvic and paraaortic lymphnode recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than chemotherapy alone, but distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Grade 3, 4, or 5 adverse events were reported in 202 patients (58%) in the chemoradiotherapy group and 227 patients (63%) in the chemotherapyonly group. CONCLUSIONS Chemotherapy plus radiation was not associated with longer relapsefree survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma.