AIM: We performed a meta-analysis of epidemiological studies evaluating exposure to pioglitazone and the risk for bladder cancer and compared these results to the drug's effects on cardiovascular disease (CVD) and non-alcoholic steatohepatitis (NASH). METHODS: Pubmed and Embase were searched for cohort and case control studies for all years through 2016. RESULTS: Data from 17 papers were analyzed. In cohort studies, 822 of 357,888 pioglitazone-exposed patients (0.23%) developed bladder cancer while 7691 of 2,898,682 unexposed (0.26%) did. In case control studies, 3219 of 1,146,916 patients (0.28%) developed bladder cancer. A random effects model showed no significant association between ever vs never use or with cumulative doses of pioglitazone. However, there was a significant association with 1-2 years (HR = 1.28 [1.08-1.55]) and >2 years (HR = 1.42 [1.14-1.77]) of exposure. The numbers needed to treat for one additional case of bladder cancer ranged from 899 to 6380 while to benefit CVD and NASH, 4-256 and 2-12, respectively. CONCLUSIONS: Given the very small prevalence of bladder cancer in diabetic patients exposed (or not) to pioglitazone (<0.3%) and the much greater beneficial effects of the drug on CVD and NASH, the use of pioglitazone should be resurrected.