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IntroductionChildren and young people placed in out-of-home care (OoHC) are often affected by a history of trauma and adverse childhood experiences. Trauma in early childhood can impact on children’s health and psychosocial development, whereas early interventions can improve children’s development and placement stability. Although several interventions and practice models have been developed to improve health and psychosocial outcomes for children and young people in OoHC, there remains a lack of rigorous research examining the impact of these interventions in OoHC settings, as there are no systematic reviews examining the impact these interventions and practice models have on the children and young people they serve. We aim to conduct a comprehensive systematic review to examine the effectiveness of interventions and practice models for improving health and psychosocial outcomes in children and young people living in OoHC and to identify relevant knowledge gaps.Methods and analysisMajor electronic databases including Medline, Medline in-process and other non-indexed citations, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycInfo, Sociological Abstracts and all Evidence-Based Medicine Reviews incorporating: Cochrane Database of Systematic Reviews, American College of PhysiciansJournal Club, Database of Abstracts of Reviews of Effects,Cochrane Central Register of Controlled Trials, CochraneMethodology Register, Health Technology Assessment and National Health Service Economic Evaluation Database, will be systematically searched for any studies published between 2008 and 2018 of interventions and practice models developed to improve health and psychosocial outcomes for children and young people in OoHC. Two independent reviewers will assess titles and abstracts for eligibility according to prespecified selection criteria and will perform data extraction and quality appraisal. Meta-analyses and/or metaregression will be conducted where appropriate.Ethics and disseminationThis study will not collect primary data and formal ethical approval is therefore not required. Findings from this systematic review will be disseminated in a peer-reviewed publication and conference presentations.PROSPERO registration numberCRD42019115082.