Background: Compared to cigarette smoking, e-cigarette use is likely to present a reduced risk of smoking-related disease (SRD). However, several studies have shown that vaping predicts smoking initiation and might provide a gateway into smoking for those who otherwise would never have smoked. This paper considers various aspects of the gateway issue in youths. Methods: Here, we reviewed studies (N=15) of the gateway effect examining how extensively they accounted for confounders associated with smoking initiation in youths. We estimated how omitting a confounder, or misclassifying it, might bias the association between vaping and smoking initiation. We assessed how smoking prevalence might be affected by any true gateway effect, and examined trends in youth smoking and e-cigarette use from national surveys. Results: The list of smoking predictors adjusted for in studies reporting a significant gateway effect is not comprehensive, rarely considering internalising/externalising disorders, outcome expectancies, school performance, anxiety, parental smoking and peer attitudes. Furthermore, no study adjusted for residual confounding from inaccurately measured predictors. Better adjustment may substantially reduce the estimated gateway effect. Calculations showed that as any true gateway effects increase, there are much smaller increases in smoking prevalence, and that gateway effects increase only if initiating vaping is more frequent than initiating smoking. These effects on prevalence also depend on the relative odds of quitting vs. initiation. Data from five surveys in US/UK youths all show that, regardless of sex and age, smoking prevalence in 2014–2016 declined faster than predicted by the preceding trend, suggesting the absence of a substantial gateway effect. We also present arguments suggesting that even with some true gateway effect, introducing e-cigarettes likely reduces SRD risk. Conclusions: A true gateway effect in youths has not yet been demonstrated. Even if it were, e-cigarette introduction may well have had a beneficial population health impact.