Racial differences in diabetes-associated pancreatic cancer (PC) and the interaction of diabetes with other risk factors are not well established. We determined the association between diabetes and risk of PC in 2,192 cases and 5,113 controls in three large case-control studies conducted at the National Cancer Institute, the University of California San Francisco, and the M.D. Anderson Cancer Center. In multivariable analyses, diabetes was associated with a 1.8-fold risk of PC [95% confidence interval (CI) = 1.5-2.1]. Risk estimates decreased with increasing years with diabetes (≤2 years OR = 2.9, 95% CI = 2.1-3.9; 3-5 years OR = 1.9, 95% CI = 1.3-2.6; 6-10 years OR = 1.6, 95% CI = 1.2-2.3; 11-15 years OR = 1.3, 95% CI = 0.9-2.0; > 15 years OR = 1.4, 95% CI = 1.0-2.0 (p for trend < 0.0001). Among diabetics, risk was higher in insulin ever users compared with nonusers (OR = 2.2, 95% CI = 1.6-3.7) and was restricted to insulin use of ≤3 years (OR = 2.4). Insulin use of >10 years was associated with a reduced risk of pancreatic cancer (OR = 0.5, 95% CI = 0.3-0.9; p for trend < 0.0001). Hispanic men and Asians had a higher risk of diabetes-associated PC than did whites and blacks, but the differences were not statistically significant. No significant interaction between diabetes and cigarette smoking, alcohol consumption and body mass index was observed. Although reverse causation may explain the association between diabetes diagnosed in close temporal proximity to PC, our results show that long-term diabetes, even though risk diminishes over time, remains a risk factor for PC independent of obesity and smoking.