OBJECTIVES: While diabetes has been linked to several cancers in the gastrointestinal (GI) tract, findings have been mixed for sites other than colorectal and liver cancer. We used the Women's Health Initiative (WHI) data and conducted a comprehensive assessment of associations between diabetes and GI malignancy (esophagus, stomach, liver, biliary, pancreas, colon, and rectal). METHODS: A total of 145,765 postmenopausal women aged 50-79 enrolled in the WHI were followed for a mean 10.3 years. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between GI cancers and diagnosed diabetes, including its duration and treatment. RESULTS: Diabetes at enrollment was associated with increased risk of liver (HR = 2.97; 95 % CI, 1.66-5.32), pancreatic (HR = 1.62; 95 % CI, 1.15-2.30), colon (HR = 1.38; 95 % CI, 1.14-1.66), and rectal (HR = 1.87, 95 % CI: 1.22-2.85) cancer. Diabetes severity, assessed by duration or need for pharmacotherapy, appeared to have stronger links to risk of liver, pancreatic, and rectal cancer, but not colon cancer. There was no statistically significant association of diabetes with biliary, esophageal, and stomach cancers. CONCLUSION: Type 2 diabetes is associated with a significantly increased risk of cancers of the liver, pancreas, colon, and rectum in postmenopausal women. The suggestion that diabetes severity further increases these cancer risks requires future studies.