The apparently smaller LDL cholesterol (LDL-C)-lowering effect of soy in recent studies has prompted the U.S. FDA to reexamine the heart health claim previously allowed for soy products. We therefore attempted to estimate the intrinsic and extrinsic (displacement) potential of soy in reducing LDL-C to determine whether the heart health claim for soy continues to be justified. The intrinsic effect of soy was derived from a meta-analysis using soy studies (20-133 g/d soy protein) included in the recent AHA Soy Advisory. The extrinsic effect of soy in displacing foods higher in saturated fat and cholesterol was estimated using predictive equations for LDL-C and NHANES III population survey data with the substitution of 13-58 g/d soy protein for animal protein foods. The meta-analysis of the AHA Soy Advisory data gave a mean LDL-C reduction of 0.17 mmol/L (n = 22; P < 0.0001) or 4.3% for soy, which was confirmed in 11 studies reporting balanced macronutrient profiles. The estimated displacement value of soy (13-58 g/d) using NHANES III population survey data was a 3.6-6.0% reduction in LDL-C due to displacement of saturated fats and cholesterol from animal foods. The LDL-C reduction attributable to the combined intrinsic and extrinsic effects of soy protein foods ranged from 7.9 to 10.3%. Thus, soy remains one of a few food components that reduces serum cholesterol (>4%) when added to the diet.