BackgroundElectronic cigarettes (e-cigarettes) are being advertised and sold with synthetic nicotine. Little research has examined youth awareness of synthetic nicotine or the impact of synthetic nicotine descriptors on perceptions of e-cigarettes.MethodsParticipants were a sample of 1603 US adolescents (aged 13–17 years) from a probability-based panel. The survey assessed knowledge of nicotine source in e-cigarettes (from ‘tobacco plants’ or ‘other sources besides tobacco plants’) and awareness of e-cigarettes containing synthetic nicotine. Then, in a between-subjects experiment with a 2×3 factorial design, we manipulated descriptors on e-cigarette products: (1) nicotine label (inclusion of the word ‘nicotine’: present or absent) and (2) source label (inclusion of a source: ‘tobacco-free’, ‘synthetic’ or absent).ResultsMost youth were either unsure (48.1%) or did not think (20.2%) that nicotine in e-cigarettes comes from tobacco plants; similarly, most were unsure (48.2%) or did not think (8.1%) that nicotine in e-cigarettes comes from other sources. There was low-to-moderate awareness of e-cigarettes containing synthetic nicotine (28.7%), with higher awareness among youth who use e-cigarettes (48.0%). While no main effects were observed, there was a significant three-way interaction between e-cigarette status and the experimental manipulations. The ‘tobacco-free nicotine’ descriptor increased purchase intentions relative to ‘synthetic nicotine’ (simple slope: 1.20, 95% CI 0.65 to 1.75) and ‘nicotine’ (simple slope: 1.20, 95% CI 0.67 to 1.73) for youth who use e-cigarettes.ConclusionsMost US youth do not know or have incorrect beliefs about the sources of nicotine in e-cigarettes and describing synthetic nicotine as ‘tobacco-free nicotine’ increases purchase intentions among youth who use e-cigarettes.