To determine overall survival (OS), progression-free interval (PFI), and toxicity in patients with advanced stage or recurrent endometrial cancer (EMCA) treated with combination paclitaxel, carboplatin and megestrol acetate. Patients with stage III/IV or recurrent EMCA were enrolled between October 2004 and April 2008 and received paclitaxel (175 mg/m2) and carboplatin (AUC 6) every 21 days for 6 cycles and megestrol acetate 40 mg orally 4 times daily for up to 5 years. Dose reductions were based on grade 3/4 hematologic toxicity. Survival was calculated from time of study enrollment. A total of 28 patients were evaluable: 21 (75%) patients with stage III/IV disease and 7 (25%) with recurrent disease. Three patients with recurrence received prior radiation. Mean PFI was 40.2 months (29.7-50.6). Mean OS was 50.1 months (41.5-58.7). After a median 40.4 months (range, 5.6-68.4) of follow-up, 13 patients (46%) had no evidence of disease, 4 were alive with disease, and 10 were dead of disease. One patient died without evidence of disease. Twenty-three patients (82%) completed 6 cycles of chemotherapy. Ten patients experienced a dose reduction. Myelosuppression was common, with 22 patients (78%) experiencing grade 3/4 neutropenia and 6 patients (21%) experiencing grade 3/4 anemia. Three patients had a deep vein thrombosis. One patient experienced a pulmonary thromboembolus. Combination therapy with paclitaxel, carboplatin and megestrol acetate demonstrates activity. Myelosuppression is common but can be managed with colony-stimulating factors. The addition of hormonal therapy to cytotoxic chemotherapy may improve survival.