OBJECTIVE: There are regional differences in the burden of tuberculosis (TB). Although these differences might be explained by regional differences in the risk factors of TB, whether such risk factors are actually associated with the regional differences in the TB burden remains unclear. This study aimed to investigate the relationship between the risk factors of and regional differences in TB incidence. METHODS: A cohort study applying nationwide claims database in Republic of Korea included patients newly diagnosed with type 2 diabetes mellitus (DM) in 2009. The main outcome was the incidence of TB defined based on the diagnostic codes combined with anti-tuberculosis treatment repeated within 90 days. Sixteen regions were categorized into 3 groups according to the age- and sex-standardized TB incidence rates. Multivariate logistic regression analysis adjusted for risk factors was performed to identify the determinants of the regional differences in TB incidence. RESULTS: Among 331 601 participants newly diagnosed with type 2 DM and with no history of previous TB, 1216 TB cases were observed. The regional TB incidence rates ranged between 2.3 and 5.9/1000 patients. Multivariate analyses did not identify any determinants of regional differences in the TB incidence among the various risk factors, including age, sex, health care utilization, co-morbidities, medication and treatment and complications of DM. Similarly, temperature, humidity and latent TB infection rate also did not affect the results. CONCLUSIONS: Although substantial regional differences in the TB incidence rate were observed among patients with newly diagnosed DM, no determinants of regional difference were identified among the risk factors.