This study systematically reviews the evidence of physiological and pathophysiological cardiovascular effects after direct exposure to electronic cigarettes and discusses the implications for cardiovascular disease. Methods Four researchers conducted the review applying Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. 28 Search strategy A literature search was conducted on 17 July 2017 and updated on 12 th June 2019 using Ovid MEDLINE and Embase databases from 1996 to 11 June 2019. The following search terms were utilised: 'e-cig*' or 'electronic cig*' or 'e-liquid' or 'e-juice' or 'electronic nicotine delivery system' or 'vape' combined with 'cardi*' or 'myocardi*' or 'coronary' or 'heart' or 'vascular' or 'endotheli*'. Reference lists of included articles and pertinent policy papers were examined for additional citations and a secondary literature search was conducted through Web of Science. Inclusion, exclusion and study eligibility criteria Experimental studies pertaining to (human) in vitro, animal, or human cardiovascular effects of e-cigarette use were included. Full details are presented in Appendix 1. Studies had to report quantifiable biomarkers of cardiovascular effects or cardiovascular pathology. Nonexperimental studies were excluded but are summarised in web appendix 2. Human studies: Eligibility criteria: adults with or without cardiovascular disease, independent of smoking status and age. Data extraction and synthesis Extraction tables collated data on study, participant, and intervention characteristics together with study results. Despite the publication of a recent meta-analysis of haemodynamic outcomes from e-cigarette use, 29 we decided to synthesised extracted data narratively due to concerns about study heterogeneity. We organised our findings based on a conceptual model of potential pathways that draws on previous papers, including that developed by Middlekauff (Figure 1). 27 Conflict of interest in studies To assess any influence of conflict of interest (COI), influence not generally captured by traditional quality assessment tools, on appraisal of e-cigarettes one reviewer extracted outcome data and conclusions verbatim from included papers and another blindly judged whether results and/or conclusions were supportive of e-cigarette use. COI status was