Background: A high prevalence of dual use of e-cigarettes and conventional cigarettes has been reported across the world. Methods: A systematic search was carried out. We included original articles on any topic relevant to health, excluding mental health, in all languages. The PRISMA guidelines were followed. Both reviewers independently screened and read all publications. We compared dual use with exclusive smoking of conventional cigarettes (ESCC). Results: Fifty-two publications (49 studies) were included. Thirteen papers/10 studies were prospective. There was great heterogeneity across studies. Many methodological weaknesses, such as inaccurate exposure measurement, lack of adjustment for former tobacco consumption, and lack of significance testing were identified. Most prospective studies found dual use to be at least as harmful as ESCC. The longest follow-up was six years. Most of the best available cross-sectional studies found dual use associated with the same and, in several studies, significantly higher risk of self-reported symptoms/disease than in ESCC. The intensity of cigarette smoking seems associated with worse health. Conclusion: Existing studies indicate that dual use is at least as, or probably even more, harmful than ESCC. Due to the predominance of cross-sectional studies and the methodological weaknesses we judged the overall certainty of the evidence as low certainty.