© 2014 Informa UK, Ltd. First-line 131I-anti-CD20 radioimmunotherapy of indolent non-Hodgkin lymphoma (NHL) achieves durable remission with low toxicity. The phase II INITIAL study comprised 68 patients with follicular NHL followed up to 7 years (median 4 years) after outpatient 131I-rituximab radioimmunotherapy (RIT) in conjunction with rituximab, followed by maintenance therapy for 1 year. Baseline and 3-month 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging, analyzed according to Deauville criteria, was used to evaluate response and predict prognosis. The overall response rate at 3 months was 99%, with 88% achieving Deauville category 1-3. These satisfactory responders did not reach median time-to-next-treatment, versus a median of 29 months for a category 4-5 response (p <0.0001). Grade IV hematological toxicity (9%) was self-limited without clinical sequelae. 131I-rituximab radioimmunotherapy in newly diagnosed, advanced stage, symptomatic follicular NHL is an effective, practical and affordable alternative to existing conventional chemotherapies, with lower toxicity and durable remissions. Response assessment at 3 months by 18F-FDG PET Deauville five-point scale permits prognostic stratification.