To assess the ability of restaging positron emission tomography (PET) scanning to predict clinical outcome after first-line treatment in patients with Hodgkin's disease, we included 60 patients with histologically proven HD, who underwent whole-body [(18)F]-fluorodeoxygenase ([(18)F]-FDG)-PET studies after first-line treatment and with a follow-up of at least 1 year. Persistence or absence of residual disease on PET was related to progression-free survival (PFS) using Kaplan-Meier survival analysis. After treatment, 55 patients showed a normal [(18)F]-FDG-PET scan; 50 of 55 remained in complete remission (CR), with a median follow-up of 955 d. Only five patients relapsed (median PFS, 296 d). During follow-up in all five patients, [(18)F]-FDG-PET was the first tool that became positive for relapse. Persistent abnormal [(18)F]-FDG uptake was seen in only five patients; all of them relapsed (median PFS, 296 d). In four of five patients, only PET predicted persistent disease. All relapses were proven histologically. Two-year actuarial PFS rate for negative patients was 91% compared with 0% for positive patients. We concluded that [(18)F]-FDG-PET has an important prognostic role in the post-treatment evaluation of HD patients.