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Data suggest that adverse social determinants during adolescence can set in motion a lifetime of poor social and health outcomes. Vulnerable youths are at particularly high risk in this regard.To identify and assess the current evidence base for adolescent-focused interventions designed to influence adulthood preparation that could affect longer-term social determinants.Using a systematic review methodology, we conducted an initial assessment of intervention evaluations targeting 6 adulthood preparation subject (APS) areas to assess the quality and character of the evidence base. The review is specific to evaluated interventions that address at least 1 of the 6 APS areas: healthy relationships, adolescent development, financial literacy, parent-child communication, educational and career success, and healthy life skills.The inclusion criteria were as follows: (1) published in English in an independent, peer-reviewed journal; (2) conducted in developed, English-speaking countries; (3) implemented an intervention that addressed at least 1 of the 6 APS areas, delivered in an in-person setting; (4) included youths at the 5th- through 12th-grade levels or aged 10 to 18 years at some point during intervention implementation; (5) included an evaluation component with a comparison group and baseline and follow-up measures; (6) included behavioral measures as outcomes; and (7) reported statistical significance levels for the behavioral outcome measures.We developed an abstraction form to capture details from each article, including key details of the intervention, such as services, implementer characteristics, and timing; adulthood preparation foci; evaluation design, methods, and key behavioral measures; and results, including key statistically significant results for behavior-based outcome measures. We assessed study quality by using several key factors, including randomization, baseline equivalence of treatment and control groups, attrition, and confounding factors. We characterized the quality of evidence as high, moderate, or low on the basis of the described design and execution of the research. Our assessment included only information stated explicitly in the manuscript.A total of 36 independent intervention evaluations met the criteria for inclusion. Of these, 27 (75%) included significant findings for behavioral outcomes related to adulthood preparation. Quality was mixed across studies. Of the 36 studies reviewed, 27 used a randomized controlled design (15 group randomization, 12 individual randomization), whereas the others used observational pre-post designs. Ten studies used mixed-methods approaches. Most (n = 32) studies used self-report questionnaires at baseline with a follow-up questionnaire, and 14 studies included multiple follow-up points.Of the studies reviewed, 7 studies received a high-quality rating, indicating no significant issues identified within our quality criteria. We rated 23 studies as moderate quality, indicating methodological challenges within 1 of the quality criteria categories. The most common reasons studies were down-rated were poor baseline equivalency across treatment groups (or no discussion of baseline equivalency) and high levels of attrition. Finally, 6 studies received a low-quality rating because of methodological challenges across multiple quality domains. The studies broadly represented the APS areas. We identified no systematic differences in study quality across the APS areas.Although some of the intervention results indicate behavioral changes that may be linked to adulthood preparation skills, many of the extant findings are derived from moderate- or poor-quality studies. Additional work is needed to build the evidence base by using methodologically rigorous implementation and evaluation designs and execution.Interventions designed to help adolescents better prepare for adulthood may have the potential to affect their longer-term social determinants of health and well-being. More theory-driven approaches and rigorously evaluated interventions could strengthen the evidence base and improve the effectiveness of these adulthood preparation interventions.