Background: Juvenile delinquents constitute a heterogeneous group, which complicates decision-making based on risk assessment. Various psychosocial factors have been used to define clinically relevant subgroups of juvenile offenders, while neurobiological variables have not yet been integrated in this context. Moreover, translation of neurobiological group differences to individual risk assessment has proven difficult. We aimed to identify clinically relevant subgroups associated with differential youth offending outcomes, based on psychosocial and neurobiological characteristics, and to test whether the resulting model can be used for risk assessment of individual cases. Methods: A group of 223 detained juveniles from juvenile justice institutions was studied. Latent class regression analysis was used to detect subgroups associated with differential offending outcome (recidivism at 12 month follow-up). As a proof of principle, it was tested in a separate group of 76 participants whether individual cases could be assigned to the identified subgroups, using a prototype ‘tool’ for calculating class membership. Results: Three subgroups were identified: a ‘high risk—externalizing’ subgroup, a ‘medium risk—adverse environment’ subgroup, and a ‘low risk—psychopathic traits’ subgroup. Within these subgroups, both autonomic nervous system and neuroendocrinological measures added differentially to the prediction of subtypes of reoffending (no, non-violent, violent). The ‘tool’ for calculating class membership correctly assigned 92.1% of participants to a class and reoffending risk. Conclusions: The LCRA approach appears to be a useful approach to integrate neurobiological and psychosocial risk factors to identify subgroups with different re-offending risk within juvenile justice institutions. This approach may be useful in the development of a biopsychosocial assessment tool and may eventually help clinicians to assign individuals to those subgroups and subsequently tailor intervention based on their re-offending risk.