This study aimed at evaluating the role of consolidation radiation in a setting of Hodgkin's lymphoma (HL) patients, using event-free survival (EFS) as end point. Among 260 patients treated with induction chemotherapy for bulky HL, 160 patients achieved negative residual masses at 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) scans. They were randomly divided into two well-matched groups to receive either 32 Gy radiotherapy to bulky area or no further therapy. At a median follow-up of 40 months, histology showed a malignancy in 14% of patients in the chemotherapy-only group (HL, 11 patients) and in 4% of patients in the chemotherapy + radiotherapy group (HL, 2 patients; carcinoma in previously irradiated area, 1 patient) (P = 0.03). All the relapses in the chemotherapy-only group involved the bulky site and the contiguous nodal regions. Thus, the overall diagnostic accuracy of FDG-PET to exclude future relapses in the patients nonprotected by radiotherapy was 86% with a false-negative rate of 14%. Our study suggests that the addition of irradiation helps improve EFS in HL patients with post-chemotherapy FDG-PET-negative residual masses.