ImportanceLittle is known about the roles of advertising and parental and peer influence in e-cigarette use among US adolescents in recent years, hindering efforts to address the increasing rate of youth vaping.ObjectiveTo examine how e-cigarette advertising exposure and parental and peer e-cigarette use were associated with e-cigarette use among US adolescents.Design, Setting, and ParticipantsThis cohort study used data from waves 4 (December 2016 to January 2018), 4.5 (December 2017 to December 2018), and 5 (December 2018 to November 2019) of the Population Assessment of Tobacco and Health study, an on-going cohort study representative of the noninstitutionalized US population. Sample weights were applied to generate nationally representative estimates. Data were analyzed in January 2022.ExposuresPast 30-day e-cigarette advertising exposure, past 30-day parental e-cigarette use, and the number of best friends using e-cigarettes (none, a few, some, most, and all).Main Outcomes and MeasuresOutcomes were contemporary curiosity about using e-cigarettes and e-cigarette initiation at follow-up. Generalized estimating equations were used to estimate the weighted adjusted associations.ResultsWave 4 included 8548 adolescents; wave 4.5, 10 073 adolescents; and wave 5, 11 641 adolescents. Among adolescents in the wave 4 survey, 4425 (51.1%) were boys, 1935 (24.9%) were aged 12 years, 1105 (13.0%) were Black, 2515 (24.4%) were Hispanic, and 3702 (52.3%) were White. More than 60% of adolescents reported past 30-day e-cigarette advertising exposure at each survey. Among adolescents who had never used e-cigarettes, those who reported e-cigarette advertising exposure were more likely to feel curious about using e-cigarettes (adjusted odds ratio [aOR], 1.56 [95% CI, 1.43-1.70]) and were more likely to become ever e-cigarette users (aOR, 1.21 [95% CI, 1.05-1.41]) and current e-cigarette users (aOR, 1.42 [95% CI, 1.16-1.75]) at follow-up. Adolescents who reported having best friends using e-cigarettes were more likely to feel curious about using e-cigarettes (eg, all best friends: aOR, 4.13 [95% CI, 2.35-7.26]) and initiate e-cigarette use at follow-up (eg, among adolescents reporting all best friends use e-cigarettes, risk of ever use: aOR, 4.08 [95% CI, 1.44-11.59]; risk of current use aOR, 5.42 [95% CI, 1.49-19.72]) than adolescents who reported having no best friends using e-cigarettes.Conclusions and RelevanceThis cohort study of US adolescents found that e-cigarette advertising and peer influence were significantly associated with e-cigarette initiation. Efforts to address youth vaping need to consider peer influence and incorporate measures reducing e-cigarette advertising exposure.