Previous studies have provided limited evidence for a harmful effect of high glycemic index and dietary glycemic load on cancer. The authors analyzed associations among glycemic index, glycemic load, and risk of cancer in women and men in the National Institutes of Health-AARP Diet and Health Study. Published glycemic index values were assigned to 225 foods/food groups. Glycemic load was calculated by multiplying the glycemic index, carbohydrate content, and intake frequency of individual foods reported on a food frequency questionnaire. From 1995 through 2003, the authors identified 15,215 and 33,203 cancer cases in women and men, respectively. Cox proportional hazards models were used to estimate multivariate relative risks and 95% confidence intervals. For women and men, respectively, the relative risks for total cancer for high versus low glycemic index were 1.03 (P(trend)=0.217) and 1.04 (P(trend)=0.012) and, for glycemic load, were 0.90 (P(trend)=0.024) and 0.93 (P(trend)=0.01). Associations with total cancer held only among the overweight for glycemic index and among those of healthy weight for glycemic load. These findings suggest that glycemic index and glycemic load are not strong predictors of cancer incidence. The direction and small magnitude of associations might be explained by the manner in which high glycemic index and glycemic load track with overall diet and lifestyle patterns.