Background <p>Mental health services play a key role in caring for autistic youth given the common and often unmet mental health needs in this population. There is a pressing need to enhance the uptake and use of evidence-based interventions (EBIs) that improve mental health services for autism and optimize outcomes.&#xa0;EBIs targeting transdiagnostic or key factors relevant across autism and mental health conditions&#xa0;exist and have the potential to enhance mental health services for autism. Yet, these interventions have not been widely tested. Similarly, autism EBI training is an implementation strategy with the potential to enhance mental health service&#xa0;quality broadly given specific components and strategies incorporated into the EBI to enhance its impact and fit. This protocol paper describes a multisite study that examines the clinical and implementation effectiveness of a transdiagnostic EBI developed for autistic children compared to a non-autism transdiagnostic EBI in children’s mental health settings (Aim 1), confirms engaged clinical and implementation mechanisms (Aim 2), and examines the generalized and expanded effects of EBI training beyond autism (Aim 3).</p> Methods <p>This study will employ a hybrid type 2 effectiveness-implementation design to test <i>Unstuck and On Target,</i> an executive functioning EBI adapted for mental health services (autism EBI) and <i>Unified Protocol for Children</i> (non-autism EBI). Twenty-eight mental health programs will be randomized to an EBI condition and 224 therapists across these programs will be recruited and receive EBI training. Additionally, 224 autistic children and 224 non-autistic children, yoked to participating therapists, will be recruited as EBI recipients. This study will measure clinical (mental health symptom change) and implementation outcomes (EBI fidelity, training engagement, psychotherapy quality, reach) and clinical (executive functioning skills, emotion regulation skills) and implementation (autism self-efficacy and knowledge, perception of fit) mechanisms.</p> Discussion <p>This study will confirm the effectiveness of a promising executive functioning EBI in mental health settings as well as generate clinical knowledge about the potential of transdiagnostic interventions improve mental health outcomes for autistic children. Findings also have immense potential to demonstrate the ability of autism EBIs to enhance mental health services for autistic and non-autistic children more broadly.</p> Trial registration <p>This study is registered with Clinicaltrials.gov (NCT06651086). Registered on October 18, 2024.</p>