ABSTRACT: INTRODUCTION:Smoking prevalence remains high in some vulnerable groups, including those who misuse substances, have a mental illness, are homeless, or are involved with the criminal justice system. E-cigarette use is increasing and may support smoking cessation/reduction. METHODS:Systematic review of quantitative and qualitative data on the effectiveness of e-cigarettes for smoking cessation/reduction among vulnerable groups. Databases searched were MEDLINE, EMBASE, PsychINFO, CINAHL, ASSIA, ProQuest Dissertations and Theses, and Open Grey. Narrative synthesis of quantitative data and thematic synthesis of qualitative data. RESULTS:2628 records and 46 full texts were screened; 9 studies were identified for inclusion. Due to low quality of evidence, it is uncertain whether e-cigarettes are effective for smoking cessation in vulnerable populations. A moderate quality study suggested that e-cigarettes were as effective as nicotine replacement therapy. Four studies suggested significant smoking reduction; however, three were uncontrolled and had sample sizes below 30. A prospective cohort study found no differences between e-cigarette users and nonusers. No significant adverse events and minimal side effects were identified. Qualitative thematic synthesis revealed barriers and facilitators associated with each component of the COM-B (capability, opportunity, motivation, and behavior) model, including practical barriers; perceptions of effectiveness for cessation/reduction; design features contributing to automatic and reflective motivation; smoking bans facilitating practical opportunity; and social connectedness increasing social opportunity. CONCLUSION:Further research is needed to identify the most appropriate device types for practicality and safety, level of support required in e-cigarette interventions, and to compare e-cigarettes with current best practice smoking cessation support among vulnerable groups. IMPLICATIONS:Smoking prevalence among people with mental illness, substance misuse, homelessness, or criminal justice system involvement remains high. E-cigarettes could support cessation. This systematic review found limited quantitative evidence assessing effectiveness. No serious adverse events were identified. Qualitative thematic synthesis revealed barriers and facilitators mapping to each component of the COM-B (capability, opportunity, motivation, and behavior) model, including practical barriers; perceived effectiveness; design features contributing to automatic and reflective motivation; smoking bans facilitating practical opportunity; and social connectedness increasing social opportunity. Further research should consider appropriate devices for practicality and safety, concurrent support, and comparison with best practice smoking cessation support.