Importance  Electronic cigarette use (vaping) among adolescents and young adults is common. Few treatments have been tested in this population.

Objective  To evaluate the efficacy of varenicline for nicotine vaping cessation in youth who do not smoke tobacco regularly.

Design, Setting, and Participants  A 3-group randomized clinical trial compared 12 weeks of double-blind varenicline vs placebo, each added to brief, remotely delivered behavioral counseling and compared with single-blind enhanced usual care, with monthly follow-up to 24 weeks. The trial was conducted among youth, aged 16 to 25 years, who vaped nicotine daily or near daily, did not regularly smoke tobacco, and wanted to reduce or quit vaping, in a single US state from June 2022 to May 2024. Data collection ended May 28, 2024.

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