Thyroidectomy is one of the most frequently performed surgical procedure worldwide, even if the risks of lethal postoperative complications prevented its evolution and diffusion until the beginning of the XX century. At that time, T. Kocher described his meticulous technique, reporting excellent results in terms of mortality and morbidity. At present, mortality for this procedure approaches 0% and overall complication rate is less than 3%. Nonetheless, major complications of thyroidectomy (i.e. compressive hematoma, recurrent laryngeal nerve palsy and hypoparathyroidism) are still fearful complications and account for a significant percentage of medico-legal claims. Patients volume and surgical skill play an important role in reducing the risk of complications. Accurate knowledge of anatomy and pathophysiology, complications incidence and pathogenesis and a careful surgical performance are essential. In this review, post-thyroidectomy complications basing on literature analysis and personal experience are described. The main anatomical, technical and pathophysiological factors that help preventing post-thyroidectomy complications are analyzed, taking into proper account new technologies and the minimally invasive surgical procedures that influenced thyroid surgery during the last decade.