Background <p>E-cigarettes can contain either “tobacco derived” nicotine, which is comprised of almost entirely S-nicotine isomers, or “synthetic” nicotine, which is comprised of a mixture of R- and S-nicotine isomers (“R/S” nicotine). Emerging studies suggest R/S nicotine may be less pharmacologically potent, which could indicate a lower addictive potential. The purpose of the present study was to examine whether e-cigarette brands containing different nicotine types are associated with the continuation of youth’s e-cigarette use.</p> Methods <p>Data came from a prospective cohort study of youth. Analyses were restricted to youth (ages 16–24; <i>N</i> = 216) who, at their baseline assessment in 2021, were using either JUUL (S-nicotine) or Puff Bar (R/S nicotine) e-cigarettes. Multivariable logistic regression tested whether nicotine type at baseline was associated with past-30-day e-cigarette use at the 12-month follow-up.</p> Results <p>Compared to participants who used Puff Bar, participants who used JUUL had higher odds of continued use at the 12-month-follow-up (aOR, 1.93, 95% CI, 1.07–3.45, <i>p</i> = 0.029).</p> Conclusion <p>Our findings suggest that, when it comes to predicting the continuation of vaping among youth who have already initiated, nicotine type (i.e., the ratio of R- and S-isomers) may play a critical role. It is encouraging that R/S nicotine may have lower addictive potential; however, tobacco control should be vigilant for marketing strategies attempting to establish R/S nicotine e-cigarettes as “starter” products for youth.</p>