Immunohistochemical staining for beta-amyloid precursor protein (betaAPP) is a well-established marker of traumatic axonal injury in adults. Recent studies have used similar techniques to evaluate nonaccidental central nervous system injury (NAI) in infants and young children. In this prospective study, we report the results of betaAPP immunohistochemistry on the brain and spinal cord in 28 pediatric cases of NAI. BetaAPP-immunoreactive axons were present in 27/28 cases. Vascular axonal injury (VAI) due to brain swelling and secondary vascular compromise was the most common pattern of betaAPP immunoreactivity and was detected in 22 of 28 cases. Traumatic axonal injury was detected in 19/28 cases, although only eight of these cases showed brainstem staining, thus fulfilling the criteria for the diagnosis of diffuse traumatic axonal injury (dTAI). TAI and VAI were both present in 16/28 cases. Isolated TAI and VAI occurred in three and five cases, respectively. All children with isolated VAI were <18 months of age. An additional finding highlighted by betaAPP immunostaining was a penumbra of axonal injury adjacent to focal lesions, such as lacerations. We conclude that betaAPP immunohistochemistry aids in documenting trauma in nonaccidental central nervous system injury in infants and young children and that VAI is a common finding.