BACKGROUND: Diabetes is an emerging public health issue in the US, affecting 11% of Americans over the age of 20, with long-term complications that include cardiovascular disease, retinopathy, neuropathy, and nephropathy. A recent meta-analysis found that bladder cancer incidence was approximately 40% higher in individuals with diabetes; however, few studies considered duration or type of therapy and had limited adjustment for potentially confounding factors. METHODS: To further investigate the potential role of diabetes in risk of bladder cancer, the authors analyzed data from a case-control study conducted in New Hampshire in which patients with bladder cancer, and controls sampled from the population, completed an interview regarding history of diabetes, cigarette smoking history, height, weight, and history of urinary tract infections. RESULTS: The study consisted of 331 cases and 263 controls on whom information regarding diabetes was ascertained. History of diabetes was related to an increased bladder cancer risk (adjusted odds ratio = 2.2, 95% CI, 1.3 to 3.8). The association was strongest in those who had diabetes for the longest duration (OR for 16 or more years = 3.6, 1.1 to 11.2) and in those taking oral hypoglycemic medications (OR = 3.3, 1.5 to 7.1). CONCLUSIONS: Our findings support an association between bladder cancer incidence and diabetes, and further suggest that the risk may be greater among patients taking oral hypoglycemics and those with diabetes of longer duration.