Abstract Background We investigated the risk of thyroid disorders, namely hypothyroidism, thyrotoxicosis and thyroiditis, in head and neck cancer patients undergoing multimodal treatment. Methods A cohort study design using Taiwan’s National Health Insurance Research Database was used to assess head and neck cancer patients over 20 years old. The cohort was divided into one group who underwent primary tumor excision only (PTE) and another with additional neck dissection (PTE + ND). The tumor sites were stratified to estimate the tumor-site-specific risk of thyroid disorders. The effect of subsequent resurgery, radiotherapy (RT), chemotherapy (CT), and concomitant (CCRT) or sequential chemoradiation therapy (sequential CT+ RT) on the risk of thyroid disorders was explored. Results For 1999–2012, 7460 patients who underwent PTE + ND and 3730 who underwent PTE were enrolled and followed-up until the end of 2013. There were 122 and 50 patients in the two groups, respectively, who developed thyroid disorders, with no statistical difference between the groups. Patients with hypopharyngeal, oropharyngeal, or laryngeal cancer in the PTE + ND group had a higher risk of thyroid disorders (adjusted HR: 1.50, 95% CI: 0.67–3.38) than those in the PTE group when adjusted for covariates and mortality. Patients who underwent subsequent RT (adjusted HR: 3.64, 95% CI: 1.05–2.77) and CCRT (adjusted HR: 1.70, 95% CI: 1.05–2.77) after PTE + ND had a significantly higher risk of thyroid disorders. Conclusion RT results in a major risk of subsequent thyroid disorders, and ND may exacerbate this effect. Physicians should monitor thyroid function from two years after treatment initiation, especially in patients who undergo ND and subsequent RT.