To validate the simplest approach to preparing patients with differentiated thyroid carcinoma (DTC) for (131) I-administration ((131) I-A), minimizing the impact of hypothyroidism. Panel study. Ninety patients with DTC were enrolled in the study. Sixty (Group A) underwent total thyroidectomy (TT); L-T4 was not administered in preparation for (131) I-A planned for 3 weeks later. Thirty patients (Group B) with previous TT and (131) I-A stopped L-T4 in preparation for clinical evaluation, including whole-body scanning (WBS)/radioiodine therapy during thyrotrophin (TSH) stimulation planned for 3 weeks (or more) later. Thyrotrophin was measured the day before TT for group A, during L-T4 for group B (baseline-time 1) and then every week until it reached ≥ 30 mIU/l (time 2). Quality of life (QoL) was evaluated by Billewicz index. At week 3, 100% of patients in group A and 56.6% of group B exceeded TSH > 30 mIU/l. In group B, the cut-off was achieved in four patients at the fourth week (TSH 38.6 ± 8.7 mIU/l), in 3 at the fifth (53.2 ± 3) and in 6 at the sixth (42.3 ± 6.1). From time 1 to time 2, total QoL scores were less affected in group A (percentage decrease: 105%) than in group B (218%). At time 2, the total score was >+19 in group A in 46 patients and in 30 in group B. In group A, TSH levels in the higher tertile of QoL (61 ± 6 mIU/l) were not different from those in the lower tertile (62.3 ± 11.1)(P > 0.1); similar results were seen in group B (69.3 ± 13.3 vs 62.9 ± 13.1)(P > 0.1). There was a positive correlation between the time to obtain TSH ≥ 30 mIU/l and total QoL scores. Quality of life scores were not affected by thyrotrophin was measured the day before TT levels as absolute values. A longer time to obtain TSH ≥ 30 mIU/l was positively correlated with worse scores of QoL. We suggest 3 weeks without therapy can be used as an easy schedule in patients who undergo TT for DTC.