Although levothyroxine is widely used to suppress thyrotropin (TSH) levels in patients with thyroid cancer, there is no consensus on the optimal concentration of TSH to reduce the risk of disease recurrence and reduce the toxic effects due to subclinical hyperthyroidism. The purpose of this study was to evaluate the benefit of TSH suppressive therapy in patients with differentiated thyroid cancer and its toxic effects on the heart and bone. A total of 771 patients (569 females) with thyroid cancer at low to moderate risk of ATA recurrence who underwent total thyroidectomy at a tertiary care hospital between 2000 and 2006, with a mean age of 48±14 years and a median follow-up time of 6.5 years, were enrolled in the study. All patients were divided into two groups: the TSH-suppressed group (median TSH ≤ 0.4 mIU/L) and the non-TSH-suppressed group (median TSH > 0.4 mIU/L). The incidence of disease recurrence, postoperative atrial fibrillation and osteoporosis was evaluated in these two groups, the latter only in female patients. Disease recurrence occurred in 5.6% (43/771) of patients, postoperative osteoporosis was diagnosed in 3.9% (29/739) of patients, and postoperative atrial fibrillation was diagnosed in 2.3% (17/756) of patients. Although the rate of postoperative recurrence was similar in both groups (TSH-inhibited and non-inhibited) (HR 1.02, p=0.956, [CI 0.54-1.91]), the risk of postoperative AF with osteoporosis was higher in the TSH-inhibited group than in the non-TSH-inhibited group (HR 2.1, p=0.05, [CI 1.001-4.3]). Although the risk of developing AF alone was not statistically different between the two groups (HR 0.78, p=0.63, [CI 0.3-2.1]), the incidence of postoperative osteoporosis was higher in female patients in the TSH-inhibited group than in female patients in the non-TSH-inhibited group (HR 3.5, p=0.023, [CI 1.2-10.2]). The increased risk of postoperative osteoporosis disappeared when the median TSH concentration was maintained near 1 mIU/L. Instead of modifying the risk of tumor recurrence in low-risk thyroid cancer patients with ATA, TSH suppressive therapy significantly increased the risk of postoperative osteoporosis. Therefore, follow-up interventions should focus on how to avoid causing harm to patients with inert disease.