Severe psychosocial deprivation in early childhood experienced by institutionally reared children changes the course of structural brain development. Evidence from the Bucharest Early Intervention Project (BEIP) has demonstrated a causal association of random assignment to high-quality foster care intervention in early childhood with remediation of adolescent structural brain development. To date, however, caregiving quality has not been examined as a mechanism contributing to these neurodevelopmental changes. Moreover, further delineating the effects of developmental timing of high-quality caregiving experiences on neural development is critical to inform intervention for early psychosocial deprivation. In the present study, early childhood caregiving quality was examined as a mechanism underlying foster care intervention and adolescent brain structure among ever-institutionalized youth in the BEIP. Additionally, we examined the effect of the developmental timing of high-quality caregiving experiences across development on adolescent brain structure in both ever- and never-institutionalized youth. In Analysis 1, we observed a significant indirect effect of high caregiving quality following random assignment to the foster care intervention on cortical thickness in the left inferior frontal gyrus and surface area in the right lateral occipital cortex at Age 16. In Analysis 2, the earliest caregiving experiences were uniquely and consistently associated with adolescent cortical thickness. However, high-quality caregiving experiences across childhood and adolescence were associated with adolescent cortical surface area in distinct regions. Taken together, findings suggest that high-quality caregiving experiences across development, but especially in early childhood, can influence adolescent cortical structure even when accounting for experiences of caregiving adversity.