ABSTRACT: Electronic cigarette (e-cigarette) use is associated with smoking initiation among young people; however, it is also possible that smoking is associated with e-cigarette initiation. This study explores these associations among young people in Great Britain.A longitudinal survey of 1,152 11- to 18-year-olds was conducted with baseline in April 2016 and follow-up between August and October 2016. Logistic regression models and causal mediation analyses assessed whether (1) ever e-cigarette use and escalation were associated with smoking initiation (ever smoking at follow-up) among baseline never smokers (n?=?923), and (2) ever smoking and escalation were associated with e-cigarette initiation (ever e-cigarette use at follow-up) among baseline never e-cigarette users (n?=?1,020).At baseline, 19.8% were ever smokers and 11.4% were ever e-cigarette users. Respondents who were ever e-cigarette users (vs. never users, 53% vs. 8%, odds ratio [OR]?=?11.89, 95% confidence interval [CI]?=?3.56-39.72) and escalated their e-cigarette use (vs. did not, 41% vs. 8%, OR?=?7.89, 95% CI?=?3.06-20.38) were more likely to initiate smoking. Respondents who were ever smokers (vs. never smokers, 32% vs. 4%, OR?=?3.54, 95% CI?=?1.68-7.45) and escalated their smoking (vs. did not, 34% vs. 6%, OR?=?5.79, 95% CI?=?2.55-13.15) were more likely to initiate e-cigarette use. There was a direct effect of ever e-cigarette use on smoking initiation (OR?=?1.34, 95% CI?=?1.05-1.72), and ever smoking on e-cigarette initiation (OR?=?1.08, 95% CI?=?1.01-1.17); e-cigarette and smoking escalation, respectively, did not mediate these effects.Among young people in Great Britain, ever e-cigarette use is associated with smoking initiation, and ever smoking is associated with e-cigarette initiation.