A prospective multisite study examined organizational climate and structure effects on the behavior and functioning of delinquent youths with and without co-occurring substance use treated with an evidence-based treatment (EBT) for serious antisocial behavior (i.e., Multisystemic Therapy). Participants were 1,979 youths treated by 429 therapists across 45 provider organizations in North America. Results of Mixed Effects Regression Models showed some aspects of climate and structure had no effects, some had similar effects, and some had slightly differential and sometimes counterintuitive effects on the outcomes of these youths. Implications are considered for research to increase the array and availability of effective treatments for youths with co-occurring substance use across service sectors. (Contains 4 tables.)