Purpose: To provide more mature data on the efficacy and complications of a brief, dose-intense chemotherapy regimen plus radiation therapy (RT) to bulky disease sites for locally extensive and advanced-stage Hodgkin's disease. Patients and Methods: One hundred forty-two patients with stage III or IV or locally extensive mediastinal stage I or II Hodgkin's disease received Stanford V chemotherapy for 12 weeks followed by 36-Gy RT to initial sites of bulky (≥ 5 cm) or macroscopic splenic disease. Freedom from progression (FFP), overall survival (OS), and freedom from second relapse (FF2R) were determined using life-table estimates. Outcomes were analyzed according to the international prognostic score. Late effects of treatment were recorded in follow-up. Results: With a median follow-up of 5.4 years, the 5-year FFP was 89% and the OS was 96%. No patient progressed during treatment, and there were no treatment-related deaths. FFP was significantly superior among patients with a prognostic score of 0 to 2 compared with those with a score of 3 and higher (94% v 75%, P < .0001). No secondary leukemia was observed. To date, there have been 42 pregnancies after treatment. Among 16 patients who relapsed, the FF2R was 69% at 5 years. Conclusion: These data confirm our preliminary report that Stanford V chemotherapy with RT to bulky disease sites is highly effective in locally extensive and advanced Hodgkin's disease. It is most important to compare this approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the ongoing intergroup trial (E2496) to determine whether Stanford V with or without RT represents a therapeutic advance.