Ewing sarcoma (ES) mainly affects children and adolescents; thus, treatment protocols for adult patients are adapted from pediatric protocols. Long treatment durations often lead to treatment discontinuation for adults. This single-center retrospective study evaluated real-world outcomes and compliance with standard chemotherapy regimens in adult patients with localized ES. Adult patients diagnosed with localized ES who underwent curative intent treatment between 2007 and 2022 were retrospectively analyzed. Patients who were intended to receive the vincristine, adriamycin, and cyclophosphamide (VAC)/(ifosfamide, etoposide) regimen, consisting of 18 cycles along with local treatment, were included in this study. Adherence to the treatment protocol and outcomes were evaluated. Event-free survival (EFS) and overall survival were calculated, and predictors of treatment completion were assessed. A total of 31 patients were analyzed. Median age was 28 years (range, 18-71 yr); 17 patients were male (54.8%) and 14 were female (45.2%). Fourteen (45.1%) patients underwent surgery, 10 (32.3%) received radiotherapy, and 7 (22.5%) received both treatments. Eighteen (58.1%) patients completed 18 chemotherapy cycles. Patients undergoing surgical resection were likelier to complete all the chemotherapy cycles (odds ratio: 0.117, 95% confidence interval: 0.016-0.835). The estimated 5-year EFS and overall survival rates were 37% and 58%, respectively. Multivariate analysis identified a neutrophil-lymphocyte ratio >= 5 as an independent predictor of EFS (hazard ratio: 4.50, 95% confidence interval: 1.52-13.30, P = .006). Compliance with the 51-week-long vincristine, adriamycin (doxorubicin), and cyclophosphamide/ifosfamide and etoposide chemotherapy regimen remains a critical issue for adult patients. Our findings suggest that surgical resection may be associated with better compliance with the chemotherapy protocol, and a neutrophil-lymphocyte ratio of >= 5 may be linked to poorer outcomes.