WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT •Pioglitazone is mainly used in combination with diet and exercise and other anti-diabetic medications to treat type 2 diabetes mellitus. •Long term use of pioglitazone (>24 months of therapy) may be associated with an increased risk of bladder cancer. WHAT THIS STUDY ADDS •In this study population, pioglitazone does not appear to be significantly associated with an increased risk of bladder cancer in patients with type 2 diabetes. AIM To examine whether exposure to pioglitazone use is associated with increased incidence of bladder cancer in patients with type 2 diabetes mellitus. METHOD A cohort study was done in the General Practice Research Database (GPRD) between 2001 and 2010. Two hundred and seven thousand seven hundred and fourteen patients aged =40years with type 2 diabetes were studied (23548 exposed to pioglitazone and 184166 exposed to other antidiabetic medications but not pioglitazone). The association between pioglitazone and risk of bladder cancer was assessed by a Cox regression model. A propensity score matched analysis was done in a group of patients without missing baseline characteristics data. RESULTS Sixty-six and 803 new cases of bladder cancer occurred in the pioglitazone and other group, respectively (rates of 80.2 (95% CI 60.8, 99.5) and 81.8 (95% CI 76.2, 87.5) per 100000 person-years respectively). Pioglitazone did not increase the risk of bladder cancer significantly compared with the other antidiabetic drugs treatment group, (adjusted hazard ratio (HR), 1.16, 95% CI 0.83, 1.62). In a matched propensity score analysis in which both groups had similar baseline characteristics (17249 patients in each group), the adjusted HR was 1.22 (95% CI 0.80, 1.84). CONCLUSION The results suggest that pioglitazone may not be significantly associated with an increased risk of bladder cancer in patients with type 2 diabetes.