Axonal injury is a common finding in serious head injuries in infancy and those associated with non-accidental causes. This study represents the first detailed research into the biomechanics of axonal injury specifically in infants. We investigated the material properties of infant brain tissue, thresholds for axonal injury in the infant, and the loads associated with accidental and inflicted pediatric head injures. Brain tissue properties show significant age-dependence, with infant tissue being approximately twice as stiff as adult tissue. Locations of axonal injury in 3–5 day-old piglets subjected to purely inertial, non-impact rotations were compared with tissue deformations predicted by finite element simulations. Peak maximum principal strain (pkE1) was the best overall predictor of axonal injury and the optimal pkEI threshold of 33% for axonal injury in the infant is higher than previous thresholds reported for adult axonal injury. To investigate the loading conditions in accidental and inflicted pediatric head injuries, we constructed a 1.5 month infant anthropomorphic surrogate. Vigorous shakes of this infant model had similar inertial loads experienced during minor falls, but inflicted impacts were significantly higher than even a 1.5m fall onto concrete. A 3-D finite element model of a 1 month old infant head, infant material properties, axonal tissue injury thresholds and typical loading conditions were combine to determine the incidence of axonal injury during abusive and accidental events. Shakes and moderate inflicted impact scenarios produced higher strains and stresses than the fall simulation but less than 1% of the brain volume was predicted to have axonal injury. The severe inflicted impact resulted in the largest strains and stresses predicted within the brain tissue of all events examined. Axonal injury was predicted in 11–30% of the brain with injury occurring in the subcortical and deep white matter regions. This research supports the theory that traumatic axonal damage in the infant requires an impact to the head and shaking alone will not produce traumatic axonal injury.