AbstractIntroductionThe objective of this systematic review was to identify, report and critically appraise studies that have reported health outcomes from use of ENDS.MethodsWe conducted a systematic review of all published literature on the health impact of ENDS products from 1st January 2015 until February 1, 2020, following the PRISMA protocol, including across the databases, PubMed, Embase, Scopus and Google Scholar. Medical subject headings were used in the execution of PubMed searches.A category for the level of evidence was assigned blindly using the Centres for Evidence Based Medicine framework. A similar approach was adopted to evaluate methodological quality of each study utilizing the National Institutes for Health (NIH) Quality Assessment Tools.ResultsThe database search identified 755 studies and a further 265 were identified from other sources and reference reviews of which 37 studies met the eligibility criteria.The majority of studies were of low strength for levels of evidence including 24 (65%) cross-sectional, 1(2.7%) case-control and six (16%) case studies. There were four (11%) cohort studies and only one (2.7%) RCT. There was only one (2.7%) meta-analysis or pooled study of observational study designs; there were no pooled results of randomized controlled trials. Of 37 studies, eight (22%) studies reported on benefits, two (2%) studies were neutral, reporting on both harm and benefits, the remaining 27 (73%) reported only on harms. The quality ratings were poor (20, 54%), fair (9, 24%) and good (8, 22%).In our review ENDS use has not been shown to be causative for any CVD outcomes and has been shown to be beneficial for hypertensive patients. Switching from cigarettes to e-cigarettes resulted in reduced exacerbations of COPD, with no evidence of long-term deterioration in lung function. There was a suggestion of short-term reductions in respiratory function in asthmatics, but no increased risk of asthma in ENDS users who were never smokers. Mental Health, cancer and mortality have not been adequately studied to form any consensus with regards to health outcomes from ENDS use.ConclusionOur review suggests that the majority of studies on the use of ENDS products reported on negative health impacts with few reporting on health outcomes from switching from cigarettes to e-cigarettes. The strength of evidence and quality of the published studies overall is poor.Our review has demonstrated that ENDS use is not causative for any harmful CVD outcomes and may be beneficial for hypertensive patients. Switching from cigarettes to e-cigarettes resulted in reduced exacerbations of COPD, with no evidence of increased risk of asthma, long-term respiratory harm or deterioration in lung function. Other health outcomes such as mental health, cancer and mortality have not been adequately studied to form a consensus. However, the findings of our review did not negate the consensus held by many that ENDS use is safer than the risks posed from smoking cigarettes.Overall, our review found the research on ENDS use is not yet adequate to provide quantitative estimates about health risks. Consequently, the current body of evidence is inadequate for informing policy around tobacco harm reduction.