Prospective longitudinal studies mainly conclude on a causal role of e-cigarettes in the initiation of cigarettes in flagrant contradiction with conclusions drawn from epidemiology and other studies showing a sharp decline in cigarette use in parallel with the spread of e-cigarette use. This systematic review explores the reasons for this discrepancy. Methods. Among 84 publications on e-cigarette/cigarette association in adolescents identified in the Medline database from 2011 to 2022, 23 concern 22 never-smoker longitudinal sub-cohorts. Results. A link between e-cigarette experimentation at T1 and cigarette initiation at T2 is reported in sub-cohort analyses of never-smokers (AOR: 1.41 to 8.30). However, studies exclude 64.3% of T1 e-cigarette experimenters (because of dual-use) and 74.1% of T2 cigarette experimenters. With this study design, e-cigarettes contribute only to 5.3% of T2 cigarette experimentation, casting major doubt on the external validity of results and authors’ conclusions that e-cigarettes have a significant effect on the initiation of cigarettes (Gateway effect) at the population level. This sub-cohort design prohibits highlighting any Diversion effect, which is the most likely mechanism accounting for the competition between these two products. Conclusions. While nicotine abstinence remains the best medical option, over-regulation of e-cigarettes because of misinterpretation of longitudinal study results may be detrimental to public health and tobacco control.