The relationship between microdamage accumulation and bone fragility is not well understood. Previous work has demonstrated a positive relationship between microdamage and age in human cortical bone. Prior investigations have also demonstrated that fracture toughness decreases with age in the same bone. Based on these findings, the objective of this study was to test the hypothesis that a decrease in fracture toughness can be attributed to an increase in microdamage density. Microdamage parameters (density, surface density, and average crack length) were measured from bone taken from the shaft of the human femur and tibia and correlated with results from fracture toughness tests of the same bone. Results indicated that there was a weak but significant inverse relationship between fracture toughness and microdamage parameters for tension loading of the femur. These findings suggest that in vivo microdamage observable at the transmitted light level (100×) plays a secondary role to other contributory factors to decreased fracture toughness with age. Results also indicate that this relationship depends on bone ductility that apparently differs between the femur and the tibia. This study, in addition to prior investigations, suggests that crack size (microscopic vs. submicroscopic) and crack origin or type (in vivo vs. stress induced de novo) may influence the relationship between microdamage and bone toughness.