Background: Levothyroxine suppression of thyrotropin (TSH) is broadly applied to patients with thyroid cancer despite lack of consensus on the optimal TSH concentration necessary to reduce cancer recurrence while minimizing toxicity from subclinical hyperthyroidism. The objectives of this study were to examine the beneficial effects and the cardiac and skeletal toxicity of TSH suppression in well-differentiated thyroid carcinoma (DTC). Methods: A total of 771 patients (569 women) at ATA low or intermediate risk of recurrence, with a mean age of 48±14 years, and undergoing total thyroidectomy at a tertiary care center between 2000 and 2006 were followed for a median of six and a half years. They were divided into a suppressed TSH group (median TSH ≤0.4mIU/L) and a nonsuppressed group (median TSH >0.4mIU/L). Structural recurrence of thyroid cancer, postoperative atrial fibrillation (AF), and osteoporosis were examined in the two groups. Osteoporosis was only examined in women. Results: A total of 43/771 (5.6%) patients recurred, 29/739 (3.9%) patients were diagnosed with postoperative osteoporosis, and 17/756 (2.3 %) were diagnosed with postoperative AF. Despite similar rates of recurrence (HR 1.02, p=0.956 [CI 0.54-1.91]), patients treated to a median TSH ≤0.4mIU/L were at increased postoperative risk of a composite outcome of AF and osteoporosis (HR 2.1, p=0.05 [CI 1.001-4.3]) compared to those not suppressed. A differential risk of AF alone (HR 0.78, p=0.63 [CI 0.3-2.1]) was not detected, but postoperative osteoporosis was increased among women with a suppressed TSH compared to those not suppressed (HR 3.5, p=0.023 [CI 1.2-10.2]). The increased risk of postoperative osteoporosis disappeared when the patient's median TSH was maintained around 1mIU/L. Conclusion: TSH suppression significantly increases the risk of postoperative osteoporosis without changing tumor recurrence in ATA low- and intermediate-risk patients with DTC. Future interventions should focus on avoiding harm in indolent disease.