Hyperthyroidism, goiter and thyroiditis have been associated with complex thyroidectomy. Difficult thyroidectomies may implicate longer operating times and higher complication rates, while literature on quantification and prediction of difficulty in thyroidectomy is scant. We aim at assessing the impact of preoperative and intraoperative factors on the technical difficulty of total thyroidectomy (TT) and on the incidence of postoperative complications. We conducted a retrospective study on 197 TT from 343 thyroidectomies performed with intraoperative neuromonitoring between October 2019 and June 2022 (excluding lobectomies, nodal dissection, extra-thyroidal procedures). Operating time (surrogate of TT difficulty), postoperative hypocalcaemia, recurrent laryngeal nerve palsy and postoperative bleeding were assessed in relation to pre- and intraoperative characteristics. Vocal fold palsy(VFP) was defined as recovering < 12 months postoperatively. There were 87 thyroid cancers and 110 multinodular goiters (21 hyperfunctioning, 51 mediastinal). Median operating time was 136 min (range 51-310). Within 17.4 months overall median follow-up we recorded two transient VFPs and 12% symptomatic transient hypocalcaemia. At univariable analysis male sex (p = 0.005), BMI (p < 0.001), thyroiditis (p < 0.05), hypervascular goiter (p = 0.003) and thyroid adhesions to surrounding anatomical structures (p < 0.001) were associated with longer operating time. At multivariable analysis male male sex (p = 0.01), obesity (p = 0.001) and thyroid adhesions (p = 0.008) were factors for prolonged operating time. Above-normal anti-thyroid peroxidase antibodies correlated to transient symptomatic hypocalcemia (p < 0.001). Risk factors for complex TT were identified and did not correlate with morbidity rates. Results from this study may help optimizing operating room schedule and inform case selection criteria for training programs in thyroid surgery. Further research is required to confirm these findings.