© Chyan et al.; licensee BioMed Central Ltd. Background: Radiation to the neck has long been associated with an elevated risk of hypothyroidism development. The goal of the present work is to define dosimetric predictors of hypothyroidism in oropharyngeal cancer (OPC) patients treated with intensity-modulated radiation therapy. Methods: Data for 123 patients, with a median follow up of 4.6 years, were retrospectively analyzed. Patients with elevated thyroid-stimulating hormone levels or with a clinical diagnosis were categorized as hypothyroid. Patient demographic parameters, thyroid volume, mean thyroid dose, the percent of thyroid volume receiving minimum specified dose levels (VxxGy), and the absolute thyroid volume spared from specified dose levels (VSxxGy) were analyzed. Normal-tissue complication probability (NTCP) was also calculated using several recently published models. Results: Thyroid volume and many radiation dosimetric parameters were statistically different in the hypothyroid group. For the patients with initial thyroid volumes of 8 cc or greater, several dosimetric parameters were found to define subgroups at statistically significant lower risk of developing hypothyroidism. Patients with VS45 Gy of at least 3 cc, VS50 Gy at least 5 cc, VS50 Gy at least 6 cc, V50 Gy below 45%, V50 Gy below 55%, or mean thyroid dose below 49 Gy had a 28-38% estimated risk of hypothyroidism at 3 years compared to a 55% risk for the entire study group. Patients with a NTCP of less than 0.75 or 0.8, calculated using recently published models, were also observed to have a lower risk of developing hypothyroidism. Conclusions: Based on long-term follow up data for OPC patients treated with IMRT, we recommend plan optimization objectives to reduce the volume of thyroid receiving over 45 Gy to significantly decrease the risk of developing hypothyroidism.