PURPOSE: To evaluate the association between (131)I therapy for thyroid cancer and risk of developing primary hyperparathyroidism. METHODS: This was a nationwide population-based cohort study of patients with thyroid cancer diagnosed during the period 1997-2008. The data were obtained from the Taiwan National Health Insurance Research dataset. The cumulative (131)I dose in each patient was calculated. Hazard ratios (HRs) were calculated using a proportional hazards model to estimate the effect of (131)I therapy on the risk of developing primary hyperparathyroidism in the cohort. RESULTS: A total of 8,946 patients with thyroid cancer were eligible for the final analysis. Among these patients, 8 developed primary hyperparathyroidism during the follow-up period that represented 38,248 person-years giving an incidence rate of 20.9 per 10(5) person-years. (131)I was used in the treatment of 6,153 patients (68.8%) with a median cumulative dose of 3.7 GBq. The adjusted HRs were 0.21 (95% CI 0.02-1.86) and 0.46 (95% CI 0.10-2.10) for those receiving a cumulative (131)I dose of 0.1-3.6 GBq and ≥3.7 GBq, respectively, compared to no therapy. The risk of developing primary hyperparathyroidism did not increase with increasing (131)I dose (test for trend p = 0.51). No interaction was found between (131)I dose and age (p = 0.94) or (131)I dose and sex (p = 0.99). CONCLUSION: (131)I treatment for thyroid cancer did not increase risk of primary hyperparathyroidism during a 10-year follow-up in this study population. Further research with a longer follow-up period is needed to assess late adverse effects beyond 10 years.