Purpose In the ESTIMABL phase III trial, the thyroid ablation rate was equivalent for the two thyroid-stimulating hormone (TSH) stimulation methods (thyroid hormone withdrawal [THW] and recombinant human TSH [rhTSH]) and the two iodine-131 (I-131) activities (1.1 or 3.7 GBq). The objectives of this article were to present health-related quality-of-life (HRQoL) results and a cost-effectiveness evaluation performed alongside this trial. Patients and Methods HRQoL and utility were longitudinally assessed, from random assignment to the follow-up visit at 8 +/- 2 months for the 752 patients with thyroid cancer, using the Short Form-36 and the EuroQoL-5D questionnaires, respectively. A cost-effectiveness analysis was performed from the societal perspective in the French context. Resource use (hospitalization for I-131 administration, rhTSH, sick leaves, and transportation) was collected prospectively. We used the net monetary benefit approach and computed cost-effectiveness acceptability curves for both TSH stimulation methods and I-131 activities. Sensitivity analyses of the costs of rhTSH were performed. Results At I-131 administration, THW caused a clinically significant deterioration of HRQoL, whereas HRQoL remained stable with rhTSH. This deterioration was transient with no difference 3 months later. rhTSH was more effective than THW in terms of quality-adjusted life-years (QALYs; +0.013 QALY/patient) but more expensive (+(sic)474/patient). The probability that rhTSH would be cost effective at a (sic)50,000/QALY threshold was 47% in France. The use of 1.1 GBq of I-131 instead of 3.7 GBq reduced per-patient costs by (sic)955 (US$1,018) but with slightly decreased efficacy (-0.007 QALY/patient). Conclusion rhTSH avoids the transient THW-induced deterioration of HRQoL but is unlikely to be cost effective at its current price. (C) 2015 by American Society of Clinical Oncology< Réduire