Background: Recurrent endometrial cancer has a poor prognosis with limited treatment options. Systemic therapy for RMEC includes chemotherapy, immunotherapy and hormonal therapy. Although studies on hormonal therapy have described modest results, agents such as megestrol acetate (megace) continue to be used mainly for low grade, ER+/PR+ve tumors in the advanced and recurrent setting. Overall response rates have been reported in the range of 20-25% with responses up to 25-35% in ER+/PR+ve tumors. Despite comparative response rates to chemotherapy, the use of hormonal therapy in clinical trials in RMEC is hampered by a lack of clear progression-free survival (PFS) data. The primary objective of this study is to determine the PFS in RMEC patients treated with progestins. Methods: A retrospective chart review on RMEC was conducted at The Ottawa Hospital with data sourced from medical records. Main inclusion criteria were a diagnosis of RMEC between 2000 and 2019, endometrioid histology, and ≥1 one line of progestin treatment. PFS was the time from initiation of progestin therapy until progression of disease (PD) by imaging, biopsy or death. Overall survival (OS) was the time from initiation of progestins until death. Median time to PFS and OS were estimated using the Kaplan-Meier method and compared using a Log-rank Test with 95% confidence interval (CI). Results: Of 2342 cases reviewed, 75 met inclusion criteria. The mean age at the time of primary diagnosis was 66.7 years and the range of follow-up was 1-199 months (mo). Sixty-six (88.0%) patients received megestrol acetate and 9 (12.0%) received a progestin alternative. The distribution of all patients by grade was: 1: 25 (33.3%), 2: 30 (40.0%) and 3: 20 (26.7%). The median PFS for all patients with grade 1 and 2 RMEC was 15.7 mo (95% CI: 8.0, 19.5), compared to 5.0 mo (3.0, 23.0) for grade 3 disease (p=0.28). The median OS for all patients with grade 1 and 2 versus grade 3 RMEC, was 25.9 mo (15.3, 40.3) versus 12.5 mo (5.7, 35.9), respectively (p=0.12). The number of patients treated with 0 and ≥1 line of chemotherapy was 34 (45.3%) and 41 (54.7%). The median PFS for patients who were naïve to chemotherapy was 17.9 mo (14.3, 27.0), compared to 6.2 mo (3.9, 14.8) for patients who had received ≥1 prior lines of treatment (p=0.09). The median OS was 29.1 mo (17.9, 61.1) for patients who were naïve to chemotherapy, versus 23.0 mo (10.5, 37.6) for patients who were previously exposed (p=0.64). Conclusions: This real-world data suggests that progestins for RMEC have comparable outcomes to other systemic therapies in chemotherapy-exposed patients. Progestins such as megestrol acetate may be considered in the design of RMEC clinical trials.