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Background Levothyroxine (LT4) is one of the most prescribed drugs in the United States; however, many patients started on LT4 after thyroidectomy suffer from symptoms of hyper- or hypo-thyroidism before achieving euthyroidism. This study aims to describe the time required for dose adjustment before achieving euthyroidism and identify predictors of prolonged dose adjustment (PDA+) after thyroidectomy. Methods This is a single institution retrospective cohort study of patients who achieved euthyroidism with LT4 therapy between 2008 and 2017 after total or completion thyroidectomy for benign disease. Patients who needed at least three dose adjustments (top quartile) were considered PDA+. Binomial logistic regression was used to identify predictors of PDA+. Results The 605 patients in this study achieved euthyroidism in a median of 116 d (standard deviation 124.9) and one dose adjustment (standard deviation 1.3). The 508 PDA− patients achieved euthyroidism in a median of 101 d and one dose adjustment. The 97 PDA+ patients achieved euthyroidism in a median of 271 d and three dose adjustments. Iron supplementation (odds ratio = 4.4, 95% confidence interval = 1.4-13.5, P = 0.010) and multivitamin with mineral supplementation (odds ratio = 2.4, 95% confidence interval = 1.3-4.3, P = 0.004) were independently associated with PDA+. Age, gender, preoperative thyroid disease, and comorbidities did not independently predict PDA+. Conclusions After thyroidectomy, achieving euthyroidism can take nearly 4 mo. Iron and mineral supplementation are associated with PDA+. This information can inform the preoperative counseling of patients and suggests that this may expedite achieving euthyroidism.