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Background This study is a nationwide population-based retrospective cohort study to investigate the risk for developing dementia in thalassemia population. Methods In a longitudinal cohort of 1 million insured people, we identified 871 thalassemia patients who were newly diagnosed between 2000 and 2004 and selected a comparison cohort of 3484 subjects without thalassemia. We analyzed the risks for thalassemia and dementia using Cox proportional hazard regression models to assess the dementia risk in thalassemia patients after adjusting for age, gender, insured amount, urbanization and comorbidities. Results The overall risks for developing dementia were 1.88-fold (95% CI = 1.10–3.21) in patients with thalassemia compared with the comparison cohort after adjusting for age, sex, insured amount, urbanization and comorbidities. The combined effects measured for patients afflicted with thalassemia and the comorbidities of diabetes, hypertension, CAD, head injury, depression, CKD, or substance-related disorder exhibited a significant association with hyperlipidemia risk compared with that measured for patients without thalassemia and without any counterpart comorbidities. In subgroup analysis, the HRs of dementia increased, from 1.69 (95% CI = 0.93–3.07) for those who had not undergone transfusion to 2.72 (95% CI = 1.09–6.78) for those experienced transfusion compared with the no thalassemia cohort (p for trend < 0.01). Conclusion Our long-term cohort study result showed that thalassemia should be considered a crucial risk factor for developing dementia. [ABSTRACT FROM AUTHOR]