Introduction: The impact of chronic asthenia after thyroidectomy has been evaluated in two previous studies comparing total thyroidectomy and hemithyroidectomy. We compared its impact on patients undergoing thyroidectomy, parathyroidectomy for primary hyperparathyroidism, and cholecystectomy., Methods: Patients recruited for surgery (233 consecutive total thyroidectomies for non-toxic multinodular goiter, Group I, 43 consecutive parathyroidectomies for primary hyperparathyroidism, group II and a sample of 43 laparoscopic cholecystectomies, group III) were compared at three times: pre-operative, 6 months after surgery, 1 year after surgery. A brief fatigue inventory (BFI) was administered to assess asthenia. We excluded intermediate or high-risk thyroid carcinomas, Grave's disease, obese patients, secondary and tertiary hyperparathyroidism, vitamin D deficiency, and acute cholecystitis. In the postoperative period, patients who had undergone complications of each surgical procedure were also excluded. Demographics, smoking, alcohol abuse, chronic diseases (renal, cardiac, pulmonary, hepatic, and diabetes mellitus), anxiety and depression were noted., Results: In Group I the significant increase of asthenia during the three periods of detection (p < 0.001) was confirmed. Renal failure further increased the risk of asthenia. In Group II, asthenia after 6 months and 1 year after surgery decreased significantly (p < 0.001). In Group III, the variations in BFI during the three periods were not significant., Conclusions: Asthenia is a frequent sequela of total thyroidectomy, also in comparison with other types of surgery. Patients undergoing thyroidectomy must be informed of the possible implications of surgery, which should be calibrated on the strict application of guidelines., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)