Background: It is well known that thyroid hormone withdrawal (THW) in thyroid cancer patients can induce a decrease in quality of life (QOL). Recombinant human thyrotropin (rh-TSH) has been used to avoid this; however, no blinded studies have ever documented the effect. Objective: To compare QOL in patients with differentiated thyroid cancer (DTC) treated with either rh-TSH or liothyronine (L-T3) THW for 10 days. Study Design: Double-blind, randomised cross-over. Patients: Fifty-six patients with DTC treated by total thyroidectomy and indication for postsurgery radioiodine (RI) ablation therapy. Intervention: Randomisation to either L-T3 and rh-TSH prior to the first RI course and following this to ingest placebo tablets and receive placebo injections before a second RI uptake measurement 4-6 months later, or to receive placebo before the primary RI ablation and active therapy 4-6 months later. Main Outcome Measures: QOL was measured by SF-36 and 2 visual analogue scale (VAS) scores at baseline and during RI therapy or RI uptake. Results: A significant difference in QOL was seen in 2 of 4 predefined SF-36 domains (7.2 and 6.6%) and 2 VAS scales (10 and 14%), favouring rh-TSH therapy. Conclusion: This is the first blinded randomised clinical trial describing the effect of rh-TSH compared to L-T3 THW on QOL in DTC patients. A significant difference was demonstrated, though smaller than described in previous non-blinded studies. © 2013 European Thyroid Association Published by S. Karger AG, Basel