For the biochemical follow up of benign thyroid nodules, some authors recommend periodic life-long measurement of thyroid stimulating hormone (TSH) to assess for the development of toxic nodules over time. The purpose of this retrospective study was to assess the incidence of thyroid dysfunction over time in patients with benign thyroid nodule(s), with a normal TSH at diagnosis and to identify any factors that may predict biochemical dysfunction over time.Medical records of patients with the diagnosis of thyroid nodule(s) between January 2011 to August 2014 were reviewed. Patients who had TSH measurement within 1 year of initial diagnostic ultrasound (US) were included.One-hundred fifty-seven patients identified with thyroid nodule(s)satisfied inclusion criteria. At a median follow-up of 45 (34-63) months, 13 (8.3%) patients developed thyroid dysfunction. The mean initial TSH in the group which developed subclinical hyperthyroidism (0.65mIU/mL), was statistically different from the group that did not develop thyroid dysfunction (1.37mIU/mL, P 0.007). More patients with TSH < 1 mIU/L developed thyroid dysfunction as compared to subjects with TSH ≥ 1 mIU/L (P 0.022). There was no significant difference in the incidence of thyroid dysfunction on the basis of gender, race, smoking status, TPO Ab positivity, and number of nodules at diagnosis.We recommend re-examining the current practice and clinical utility of frequent TSH monitoring in all patients with thyroid nodules, particularly if initial TSH level is ≥ 1mIU/L.