PROJECT SUMMARY/ABSTRACT Obesity can pose a lifelong threat to health and quality of life for many autistic people. Across the lifespan in autism, obesity prevalence is increased relative to non-autistic peers. One third of autistic adults have obesity and there are concerning associations between obesity and in-hospital mortality, risk of type II diabetes, and cardiovascular disease. Prevention in childhood should be a priority; however, ~100,000 autistic youth will transition to adulthood each year in the United States, and there is no existing comprehensive treatment for obesity designed specifically for autistic individuals transitioning to adulthood and greater independence. The overall objective of this study is to identify stakeholder-generated and testable treatment components to inform obesity intervention specifically designed for transition-age autistic youth. Comprehensive obesity treatment programs are prime candidates for the engineering-inspired Multiphase Optimization Strategy (MOST) framework that optimizes multicomponent behavioral treatment packages to expedite implementation and maximize scalability. The proposed online study, grounded in activities for the MOST Preparation Phase, will use a simultaneous exploratory mixed methods study design to gather perspectives on obesity treatment directly from transition-age autistic youth with obesity. Thirty transition-age autistic youth with obesity (16-25 years) will complete qualitative interviews to identify stakeholder-generated factors that impact obesity treatment (Aim 1). Transition-age autistic youth with obesity (N=120), caregivers of transition-age autistic youth with obesity (N=60), and clinical providers (N=60) will rate and prioritize the perceived effectiveness of obesity treatment components (e.g., diet modifications, text message prompts, parent training, goal setting) that could be included in a comprehensive obesity intervention program tailored for transition-age autistic youth (Aim 2). Then, in partnership with a Community Advisory Board, we will integrate Aim 1 qualitative and Aim 2 quantitative findings to iteratively develop a set of treatment components specifically tailored for transition-age autistic youth with obesity that can be subsequently tested in a MOST framework optimization trial. The resulting Obesity Treatment Blueprint for Transition-Age Autistic Youth will also provide initial steps toward adaptation of existing interventions that can be leveraged for use within the proposed tailored treatment package. Aligned with NICHD Scientific Theme 4, ‘Improving Child and Adolescent Health and the Transition to Adulthood,’ this program of work will meet the pressing need for effective obesity treatment to improve health and quality of life for autistic individuals across the lifespan.