This study investigated whether rosiglitazone might increase or reduce dementia risk. Taiwan’s National Health Insurance database was used to enroll a cohort of 1:1 matched-pairs of ever and never users of rosiglitazone based on propensity score from patients with new-onset type 2 diabetes during 1999-2006. The patients were alive on January 1, 2007 and were followed up for dementia until December 31, 2011. A total of 5,048 pairs of never users and ever users were identified. The incident case numbers were 127 and 121, respectively. The adjusted hazard ratio for ever versus never users was 0.895 (95% confidence interval: 0.696-1.151). The adjusted hazard ratios for the first (<12.1 months), second (12.1-25.1 months) and third (>25.1 months) tertiles of cumulative duration of rosiglitazone therapy were 0.756 (0.509-1.123), 0.964 (0.685-1.357) and 0.949 (0.671-1.341), respectively. When cumulative duration was treated as a continuous variable, the adjusted hazard ratio was 1.000 (0.992-1.008). Subgroup analyses conducted in ever users and never users of metformin and in patients diagnosed with diabetes during three different periods of time, i.e., 1999-2000, 2001-2003 and 2004-2006, all supported a neutral effect of rosiglitazone. In conclusion, rosiglitazone does not increase or redcue the risk of dementia.