Project Summary/Abstract The long-term goal of this research program is to identify negative consequences associated with e-cigarettes and other newer tobacco products, and reduce the health burden of tobacco use by developing interventions and identifying policies to reduce youth use. This proposal focuses on e-cigarette use, which has increased substantially and is now the most common nicotine product used by US youth. Our collective knowledge is not yet sufficient to identify factors that can be targeted in e-cigarette interventions, or to be sure that we understand the negative consequences of use. We propose to take advantage of the unique nature of the ABCD study, which includes regular assessments of a large, nationally representative cohort from ages 9 to 19. The design of the study will allow us to examine a range of both (1) modifiable risk factors for e-cigarette use and (2) behavioral, psychological, neurocognitive, and physiological consequences of use. The goals of this study are to prospectively test the following hypotheses: (1) e-cigarette initiation and progression in children is driven by modifiable social, contextual, and individual risk factors; (2) children who try e-cigarettes will be more likely to become users of combustible tobacco products; (3) youth e-cigarette use is associated with neural alterations and neurocognitive deficits; (4) e-cigarette use in adolescence is associated with negative health consequences. Our goals are twofold. First, we seek to identify modifiable factors among children that are associated with risk of chronic tobacco use and dependence, in order to inform intervention development. Second, we aim to delineate the extent to which e-cigarette use causes negative physical, behavioral and cognitive consequences, in order to inform policymakers who have regulatory authority over tobacco products. The overarching goal is to reduce tobacco use among youth and thus associated morbidity and mortality.