Studies have suggested that adults with gallbladder disease have increased risk of type 2 diabetes. This prospective cohort study assessed the risk of type 2 diabetes in postmenopausal women with gallbladder disease. Data from women enrolled in the Women's Health Initiative from 1993 to 2005, aged 50-79 years (mean = 63.2; standard deviation, 7.2), were analyzed. Cox proportional hazards regression models were used to estimate the risk of type 2 diabetes associated with gallbladder disease. There were 8,896 new cases of type 2 diabetes after 1,025,486 person-years of follow-up. Gallbladder disease was significantly associated with type 2 diabetes (hazard ratio = 1.52; 95% confidence interval (CI): 1.38,1.67). The observed risk of type 2 diabetes in women with both gallbladder disease and central obesity was 37% higher than expected (relative excess risk due to interaction = 0.37, 95% CI: 0.11,0.63) on the additive scale. The hazard ratios for type 2 diabetes associated with gallbladder disease were 1.25 (95% CI: 1.19,1.32) and 1.48 (95% CI: 1.34,1.63) in women with and without central obesity, respectively, on the multiplicative scale. Results of this study support further studies to determine whether interventions in older women with gallbladder disease would reduce type 2 diabetes risk, especially among those with central obesity. Future research should examine the pathophysiological basis of the association between gallbladder disease and type 2 diabetes.