Several pediatric Hodgkin lymphoma (HL) consortia have demonstrated safe omission of radiotherapy (RT) in early stage HL, whereas feasibility of omitting RT in advanced HL is still under investigation. This is a single institution retrospective analysis of 27 patients with intermediate-risk or high-risk HL (age 22 y and younger), treated with a modification of the dose-intensive OEPA-COPDAC (vincristine, etoposide, prednisone, doxorubicin—cyclophosphamide, vincristine, prednisone, dacarbazine) regimen, with radiation restricted to only sites of inadequate early response (Deauville ≥3 and/or ≤75% tumor shrinkage). Their outcome was compared with a historical cohort (n=42) treated with Stanford V or ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), who received consolidative involved-field RT. RT was omitted in 15 of 27 (56%) of patients treated with OEPA-COPDAC, majority of whom (67%) had high-risk disease. At a median follow-up of 3.1 years, the 3-year progression-free survival was 100% in patients who received OEPA-COPDAC, versus 83.3% (95% confidence interval, 68.2%-91.7%) in the historical cohort, P=0.03. Our analysis demonstrates excellent survival with omission of RT in more than 50% of patients with pediatric advanced HL, treated with a dose-intensive chemotherapy regimen. When administered, RT was restricted to only sites of inadequate early response. Results of large prospective studies are needed to validate these findings.