Hypothyroidism is a well-documented complication after treatment of head and neck cancer and is particularly significant among patients undergoing laryngectomy. The objective of this study was the identification of factors associated with the development of hypothyroidism in this population. Records of 136 patients treated with laryngectomy were retrospectively reviewed in an attempt to define a risk factor profile for patients in whom hypothyroidism is most likely to develop after laryngectomy. The Cox proportional hazards model was used to identify factors significantly related to an increased risk for development of hypothyroidism. The actuarial method was used to estimate the period of greatest risk for the development of hypothyroidism. Increased risks were found for patients who were female (P = 0.0049), received preoperative radiation therapy (P = 0.0022), had invasion of the thyroid gland by tumor (P = 0.0003), had presence of cervical metastases (P = 0.0022), and had postoperative fistula (P = 0.0095). From the actuarial method, we estimated that the period of time when patients were at greatest risk for development of hypothyroidism was between 0 and 14 months after surgical intervention. Wound complications were twice as frequent in hypothyroid patients. Perioperative awareness of risk factors associated with the development of hypothyroidism in patients undergoing laryngectomy allows for early recognition and management of hypothyroidism and may reduce the number of complications related to wound healing and fistula.