Project Summary Tobacco use is the single leading cause of preventable death, disability and disease in the United States. Adolescence is a critical developmental period to intervene as 90% of adult tobacco users initiate during this period. Use of electronic nicotine delivery system (ENDS), which are noncombustible tobacco products (e.g., e-cigarettes), has increased dramatically among youth and is associated with numerous adverse health outcomes as well as use of alcohol and other illicit substances. National guidelines recommend counseling to address tobacco use at every adolescent clinical visit; however, many at-risk adolescents do not routinely attend primary care. There are more than 1.5 million adolescent hospitalizations annually and many of these patients are at increased risk for tobacco use and tobacco-related poor health outcomes due to underlying comorbidities (e.g., mental health disorders, substance use disorders, asthma). Although evidence supports treatment of tobacco use during an adult hospitalization, no interventions have been developed or tested in the pediatric hospital setting. Based on promising theoretically-based evidence from the primary care and hospital settings, we propose to design, iteratively refine and assess implementation of a novel tobacco and ENDS use intervention for hospitalized adolescents and young adults (AYAs). We will develop the intervention to treat tobacco and ENDS use in hospitalized AYAs utilizing the 5A’s framework with motivational interviewing, pharmacotherapy and computerized decision support tools. We will iteratively refine the intervention based on key stakeholder feedback, including AYAs, parents/guardians and hospital providers. We will conduct a randomized controlled pilot study (n=144) with 3-month follow up to evaluate preliminary efficacy as well as implementation outcomes (i.e., acceptability, feasibility, fidelity). Through conduct of these formative research activities I will gain critical skills and expertise in the design and preliminary evaluation of behavioral interventions within the context of complex health care systems. We anticipate these findings will directly inform future plans for a hybrid implementation trial of the intervention to determine efficacy for short and long- term ENDS abstinence. This work is significant as it has the potential to increase screening and treatment of tobacco and ENDS use in AYAs leading to decreased rates of use and related poor health outcomes.