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Background: The Systemic Therapy for At Risk Teens (START) trial is a randomised controlled trial of multisystemic therapy (MST) compared with management as usual (MAU). The present study reports on long-term follow-up of the trial (to 60 months)., Objectives: The primary objective was to compare MST and MAU for the proportion of young people in each group with criminal convictions up to 60 months post baseline. Secondary outcomes included group comparisons of psychological and behavioural factors. An economic analysis was carried out to determine the cost-effectiveness of MST compared with MAU. Two qualitative studies were conducted to better understand the subjective experiences of the participants., Design: Primary outcomes (collected up to 60 months) were collected using a centralised police database. Secondary outcomes were evaluated using self-report questionnaires completed by both young people and parents or carers at the 24-, 36- and 48-month follow-ups. Research assistants were blind to treatment allocation., Setting: Participants were recruited from participating MST sites in nine areas of England. Secondary outcomes were typically collected within the family home., Participants: A total of 684 families were recruited into the START trial and allocated randomly to a treatment group. Of these, 487 remained in the second phase of the trial. Young people were aged, on average, 13.8 years at baseline, with 63% male and 37% female., Interventions: MST is a manualised programme for young people exhibiting antisocial behaviour and their families that uses principles from cognitive–behavioural and family therapy to provide an individualised approach. MAU content was not prespecified, but consisted of the standard care offered to young people who met eligibility for the trial., Main Outcome Measures: Young people’s offending was evaluated using the Police National Computer. Secondary measures included validated self-report measures completed by both the young person and their parent or carer. The economic evaluation took a broad perspective and outcomes were assessed in terms of quality-adjusted life-years and offending., Results: No significant differences were found in the proportion of offending between the groups (hazard ratio 1.03, 95% confidence interval 0.84 to 1.26; p  = 0.78). No differences were found between the groups on secondary outcome measures, with a few exceptions that did not hold up consistently across the follow-up period. The economic analysis did not find evidence to support the cost-effectiveness of MST compared with MAU. Outcomes from the qualitative studies suggest that families mostly felt positive about MST, and that MST was associated with greater maturity in young men., Limitations: Some intended evaluations were not possible to deliver. Selective attrition may have influenced the nature of the sample size. It is also unclear how representative the MAU services were of reality., Future Research: Recommendations are made for the evaluation of MST in populations with more severe behavioural problems, as well as for identifying and testing new moderators., Conclusions: The results of the second phase of the START trial do not support the long-term superiority of MST to MAU, but elements of the intervention may be adapted successfully., Trial Registration: Current Controlled Trials ISRCTN77132214 and London South-East REC registration number 09/H1102/55., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research ; Vol. 8, No. 23. See the NIHR Journals Library website for further project information., (Copyright © Queen’s Printer and Controller of HMSO 2020. This work was produced by Fonagy et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.)