ObjectiveTo review and summarise the current evidence on the uptake of combustible cigarette smoking following e-cigarette use in non-smokers—including never-smokers, people not currently smoking and past smokers—through an umbrella review, systematic review and meta-analysis.DesignUmbrella review, systematic review and meta-analysis.Data sourcesPubMed, Scopus, Web of Science, PsychINFO (Ovid), Medline (Ovid) and Wiley Cochrane Library up to April 2020.ResultsOf 6225 results, 25 studies of non-smokers—never, not current and former smokers—with a baseline measure of e-cigarette use and an outcome measure of combustible smoking uptake were included. All 25 studies found increased risk of smoking uptake with e-cigarette exposure, although magnitude varied substantially. Using a random-effects model, comparing e-cigarette users versus non-e-cigarette users, among never-smokers at baseline the OR for smoking initiation was 3.19 (95% CI 2.44 to 4.16, I² 85.7%) and among non-smokers at baseline the OR for current smoking was 3.14 (95% CI 1.93 to 5.11, I² 91.0%). Among former smokers, smoking relapse was higher in e-cigarette users versus non-users (OR=2.40, 95% CI 1.50 to 3.83, I² 12.3%).ConclusionsAcross multiple settings, non-smokers who use e-cigarettes are consistently more likely than those avoiding e-cigarettes to initiate combustible cigarette smoking and become current smokers. The magnitude of this risk varied, with an average of around three times the odds. Former smokers using e-cigarettes have over twice the odds of relapse as non-e-cigarettes users. This study is the first to our knowledge to review and pool data on the latter topic.PROSPERO registration numberCRD42020168596.