The purpose of this study was to evaluate prediction of prognosis after first-line radioimmunotherapy (RIT) of advanced follicular non-Hodgkin lymphoma (FL), by imaging with fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (F-18-FDG-PET/CT) three months after induction treatment by Iodine-131-rituximab (I-131-rituximab). Objective response was determined using the Deauville 5-point scale in 68 prospective clinical trial patients. Baseline F-18-FDG-PET/CT studies were used to calculate total-metabolic-tumor-volume (TMTV). Non-imaging studies included the Follicular lymphoma international prognostic index (FLIPI) and absolute baseline monocyte and lymphocyte counts. Patients were monitored for over ten years (median follow-up 59 months), and no patient was lost to follow-up. Complete response (CR) of 88% predicted excellent prognosis with median time-to-next-treatment (TTNT) not yet reached. Those patients (12%) who failed to achieve CR (Deauville 3) on F-18-FDG-PET/CT at three months had significantly poorer outcomes (p <0.0001) with a median TTNT of 41 months. Requirement for re-treatment was predicted by FLIPI and absolute baseline monocyte count but not lymphocyte count. The TTNT was accurately predicted by F-18-FDG-PET/CT Deauville response at three months following first-line therapy of FL with RIT. Early response demonstrated by imaging does, therefore, foretell prognosis in the individual FL patients.