<jats:title>Abstract</jats:title> <jats:p>Context: Thyroid carcinoma requires lifelong monitoring with serum thyroglobulin, radioactive iodine whole body scanning, and other imaging modalities. Levothyroxine (l-T4) withdrawal for thyroglobulin measurement and whole body scanning increases these tests’ sensitivities but causes hypothyroidism. Recombinant human TSH (rhTSH) enables testing without l-T4 withdrawal.</jats:p> <jats:p>Objective: Our objective was to examine the impact of short-term hypothyroidism on the health-related quality of life (HRQOL) of patients after rhTSH vs.l-T4 withdrawal.</jats:p> <jats:p>Design, Setting, and Patients: In this multicenter study, the SF-36 Health Survey was administered to 228 patients at three time points: on l-T4, after rhTSH, and after l-T4 withdrawal.</jats:p> <jats:p>Interventions: Interventions included administration of rhTSH on l-T4 and withdrawal from thyroid hormone.</jats:p> <jats:p>Main Outcome Measures: Mean SF-36 scores were compared during the two interventions and with the U.S. general population and patients with heart failure, depression, and migraine headache.</jats:p> <jats:p>Results: Patients had SF-36 scores at or above the norm for the general U.S. population in six of eight domains at baseline on l-T4 and in seven of eight domains after rhTSH. Patients’ scores declined significantly in all eight domains after l-T4 withdrawal when compared with the other two periods (P &lt; 0.0001). Patients’ HRQOL scores while on l-T4 and after rhTSH were at or above those for patients with heart failure, depression, and migraine in all eight domains. After l-T4 withdrawal, patients’ HRQOL scores were significantly below congestive heart failure, depression, and migraine headache norms in six, three, and six of the eight domains, respectively.</jats:p> <jats:p>Conclusions: Short-term hypothyroidism after l-T4 withdrawal is associated with a significant decline in quality of life that is abrogated by rhTSH use.</jats:p>