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Background: Because controversy still continuous to surround use of total thyroidectomy for the management of benign multinodular goiter, the present study aims to prospectively compare the safety and efficacy of total thyroidectomy with subtotal thyroidectomy., Methods: A total of 200 consecutive patients with benign multinodular goiter were assigned to have either total thyroidectomy (n = 105) or subtotal thyroidectomy (n = 95) based on preoperative evaluation, intraoperative macroscopic findings and nodular dissemination. The patients with no healthy tissue or nodules localized in the dorsal part of the gland, which are usually left during normal subtotal resection, were assigned to the total thyroidectomy group. Demographic details, biochemical findings, indications for operation, operating time, specimen weight, complications and hospital stay were noted., Results: There was no significant difference in the sex, hormonal status or duration of goiter between the two groups (P = 0.74, P = 0.59 and P = 0.59, respectively). The mean operating time was longer (148.52 min +/- 51.10 vs 135.10 min +/- 32.47, P = 0.03), and the mean weight of the specimens was greater (228.40 g +/- 229.91 vs 157.01 g +/- 151.23, P = 0.01) for total rather than subtotal thyroidectomy. Either temporary recurrent laryngeal nerve (RLN) palsy or hypoparathyroidism occurred in 10 (9.3%) or 12 (11.4%) of the patients undergoing total compared with six (6.3%) or nine (9.5%) of the patients undergoing subtotal thyroidectomy (P = 0.40 and P = 0.65, respectively). Either permanent RLN palsy or hypoparathyroidism was observed in one patient undergoing total thyroidectomy (P = 0.34 for each comparison). The mean hospital stay was longer in the total thyroidectomy group (2.24 days +/- 1.18 vs 1.89 days +/- 0.72 for subtotal thyroidectomy, P = 0.01)., Conclusions: The present study shows that total thyroidectomy can be performed without increasing risk of complication, and it is an acceptable alternative for benign multinodular goiter, especially in endemic regions, where patients present with a huge multinodular goiter.