Abstract: As the scarcity of published research that comprehensively and meticulously analyzed the patient, disease, and treatment factors of prognostic significance in Ewing sarcoma (EWS) in Egypt; This study aimed at assessing survival outcomes of EWS in Upper Egypt, delineating factors of prognostic significance in comparison to other leading oncology centers in Egypt and internationally. By retrospectively reviewing medical records of 85 patients with a verified diagnosis of EWS in the period from 2001 to 2015 at Pediatric and Medical Oncology Departments at South Egypt Cancer Institute; We gathered data relevant to the patient, disease, and treatment variables of the study. Survival was estimated using the Kaplan Meier method and differences between various groups were determined by log rank test. Univariable and multivariable analyses were performed using Cox regression. With a median follow-up period of 62.7 months (95% CI 52.2-73.2, SE=5.4) for the study patients, the estimates of event-free survival (EFS) and overall survival (OS) at 3 and 5 years were 42.1% and 50.6%, and 40.8% and 48.5%, respectively. Metastatic disease at initial presentation (HR=8.91, 95% CI, 4.00-19.9; P<0.0001) stood as the most powerful predictor of OS in the multivariable analysis, followed by surgery used as a local modality (HR=0.16, 95% CI, 0.06-0.44; P=0.0004). Response to neoadjuvant chemotherapy (HR=2.61, 95% CI, 1.11-6.13; P=0.028), primary tumor size (HR=2.49, 95% CI, 1.03-6.03; P=0.044) were also shown to be significantly associated with OS. Radiotherapy as a local modality, whose effect, apparently shown to increase the hazard of events occurrence in the univariable analysis, an effect that was reversed to reveal EFS advantage (HR=0.41, 95% CI, 0.18-0.95; P=0.036) after control of other variables. With 5-year OS of 48.5%, our survival results were comparable to those previously published from Egypt; however, differences still exist between centers due to varied representative study samples. However, outcomes in Egypt in general are still inferior to internationally published studies.