Traumatic brain injury (TBI) is a leading cause of death and disability in children, yet little is known regarding the pattern of TBI-related microstructural change and its impact on subsequent development. Diffusion tensor imaging (DTI) was used to examine between-group differences at two time points (planned intervals of 3 months and 18 months post-injury) and within-group longitudinal change in a group of children and adolescents aged 7-17 years with moderate-to-severe TBI (n = 20) and a comparison group of children with orthopedic injury (OI) (n = 21). In the 3- and 18-month cross-sectional analyses, tract-based spatial statistics (TBSS) generally revealed decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) in the TBI group in regions of frontal, temporal, parietal, and occipital white matter as well as several deep subcortical structures, though areas of FA decrease were more prominent at the 3-month assessment, and areas of ADC increase were more prominent at the 18 month assessment, particularly in the frontal regions. In terms of the within-group changes over time, the OI group demonstrated primarily diffuse increases in FA over time, consistent with previous findings of DTI-measured white matter developmental change. The TBI group demonstrated primarily regions of FA decrease and ADC increase over time, consistent with presumed continued degenerative change, though regions of ADC decrease were also appreciated. These results suggest that TBI-related microstructural changes are dynamic in children and continue until at least 18 months post-injury. Understanding the course of these changes in DTI metrics may be important in TBI for facilitating advances in management and intervention.