Autonomic nervous system reactivity has been posited to be a mechanism contributing to social and emotional problems among children exposed to early adversity. Leveraging data from the Bucharest Early Intervention Project, a longitudinal randomized controlled trial of foster care versus institutional care of abandoned children in Romania, we assessed whether altered sympathetic reactivity to peer rejection feedback in early adolescence mediated the relation between early institutional rearing and peer problems in later adolescence. We also assessed whether adolescent friendship quality or randomized placement in foster care early in life moderated these associations. Participants include 68 institutionalized children randomized to care as usual, 68 institutionalized children randomized to foster care, and 135 never-institutionalized children. At age 12, participants reported friendship quality with respect to a best friend and completed a social rejection task while electrocardiogram and impedance cardiography were recorded. Sympathetic nervous system reactivity to rejection feedback was assessed using preejection period (PEP). At ages 12 and 16, peer problems were reported by parents. Mediation analysis revealed that less PEP reactivity to social rejection at age 12 partially mediated the association between early institutionalization and greater peer problems at age 16. Further moderated mediation analysis revealed that this indirect effect was evidenced among previously institutionalized youths with low, but not high, quality friendships. We did not observe foster care intervention effects. These findings suggest that altered sympathetic reactivity to social rejection might be a mechanism linking early institutionalization to social difficulties into adolescence, however, positive adolescent friendships may buffer these effects. (PsycInfo Database Record (c) 2022 APA, all rights reserved).