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Objective: Young adulthood is an important transitional life phase where careers are established. Young adults with chronic disabling health conditions are underrepresented in the labour market. Our study aims to examine the effectiveness of work-focused interventions that support the labour market transition of young adults with chronic disabling health conditions; and to examine whether the effectiveness of work-focused interventions differ across work transition phase (eg, preparation, entry and sustaining work, employment advancement) and disability type.Methods: A systematic review of articles published between January 1990 and July 2018 was conducted. Medline, EMBASE and PsycInfo were searched, and titles/abstracts and full texts of articles were reviewed for eligibility. Relevant articles were appraised for methodological quality. A best evidence synthesis was applied to medium-quality/high-quality studies to develop recommendations.Results: 5816 articles were identified; 10 articles were relevant and of moderate-high methodological quality. Six intervention categories were identified which focused on young adults with mental health or intellectual/learning disabilities (n=3) and addressed employment preparation (n=10) and/or work entry (n=9). No interventions addressed at-work issues or career advancement. Strong evidence existed for tailored supported employment (SE) interventions having a positive impact on preparation and entry into competitive employment. Also, moderate evidence existed for the positive impact of SE on preparation and entry into competitive employment for young adults with mental health conditions.Conclusions: Tailored SE is recommended to foster preparation and entry into the labour market. Evidence-based interventions are needed to facilitate sustained work and career advancement of young adults living with different disabling health conditions. [ABSTRACT FROM AUTHOR]