Background. Whether rosiglitazone use in patients with type 2 diabetes may affect thyroid cancer risk has not been investigated. Methods. The reimbursement databases of all diabetic patients under oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance of Taiwan. An entry date was set at 1 January 2006, and 887,665 patients with type 2 diabetes were followed for thyroid cancer incidence until the end of 2009 for ever-users, never-users, and subgroups of rosiglitazone exposure using tertile cut-offs for time since starting rosiglitazone, duration of therapy, and cumulative dose. Hazard ratios were estimated by Cox regression. Results. There were 103,224 ever-users and 784,441 never-users, with respective numbers of incident thyroid cancer of 84 (0.08%) and 764 (0.10%), and respective incidence of 23.12 and 28.09 per 100,000 person-years. The overall multivariable-adjusted hazard ratio was not significant. However, in dose-response analyses, the adjusted hazard ratios (95% confidence intervals) were significant for the third tertile of duration of therapy (>/= 14 months) and cumulative dose (>/= 1,800 mg) for age >/= 50 years: 0.53 (0.31-0.89) and 0.50 (0.29-0.87), respectively. Conclusions. This study suggests that rosiglitazone use in patients with type 2 diabetes may reduce the risk of thyroid cancer.