Major depressive disorder (MDD), associated with a lifetime prevalence rate of 11% in adolescents, results in significant disease burden worldwide. Adolescent MDD clinical trials evaluate interventions by measuring the effects of the interventions on various treatment outcomes, such as “severity of depressive symptoms” or “social functioning.” The ability to compare or contrast treatments and to generate usable, meaningful data, however, depends on trials using well-selected and well-defined outcomes measured by validated tools. To ensure comparability between trials, core outcome sets (COS) have been developed for use in other healthcare areas, which has resulted in improved standardization of outcome selection and measurement across effectiveness trials, facilitating the synthesis of results in systematic reviews. A COS is an agreed-upon, standardized minimum set of outcomes that should be measured and reported in all clinical trials in specific areas of health, while not precluding the inclusion of other outcomes. More recently, a growing awareness of the importance of COS has led to greater patient engagement in outcome selection and measurement, resulting in a stronger emphasis on quality of life and functional outcomes as being critical to evaluate. The primary objective of this project will be to develop an evidence- and consensus-based COS for adolescent MDD clinical trials assessing any type of intervention by following COS development methodology recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Innovative adaptations to ensure engagement of youth and caregivers will be used throughout this project; thus, a secondary objective is to develop guidance for incorporating youth and family engagement in the development of COS for adolescent mental health.