E-cigarettes are thought to aid in tobacco smoking cessation, but there are concerns about their overall effectiveness and safety for the general population, particularly adults. This review aims to investigate the mechanisms of toxicity and adverse effects of e-cigarettes on the respiratory system, comparing these effects with those of conventional smoking. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were performed on PubMed, Embase, and the Cochrane Library using keywords, controlled vocabulary, and text words, with the following criteria: studies published in English from 2014 to 2024, open access, peer-reviewed, and full-text availability. Study selection, quality assessment, and data extraction were carried out by two independent reviewers. The Cochrane Risk of Bias 2.0 tool was used to evaluate the risk of bias in included randomized controlled trials, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was employed to assess the strength of evidence and determine its generalizability. Electronic nicotine delivery systems (ENDS) have diverse mechanisms of toxicity, including inflammation, hypoxia, cardiovascular stress, and metabolic changes. Reported adverse effects include cough, throat irritation, nausea, and hemodynamic changes. However, ENDS are associated with fewer risks compared to conventional cigarette smoking. ENDS users experience fewer respiratory and cardiovascular issues and have lower levels of biomarkers such as NNAL and CO compared to traditional smokers. Additionally, ENDS are more effective than nicotine replacement therapy (nicotine patches) for smoking cessation, particularly in pregnant women. The side effects of ENDS and nicotine-free vaping are similar to those of conventional smoking in pregnant women, with the exception of a lower birth weight among newborns exposed to ENDS (p < 0.05). ENDS present a complex balance of benefits and risks regarding respiratory health. While there are adverse effects, ENDS are considered less detrimental than conventional smoking and a viable option for smoking cessation. Longitudinal studies are needed to evaluate their safety with long-term use (>16 weeks). Policymakers and health practitioners should use these findings to develop balanced public health policies that weigh the benefits of ENDS against potential health risks, enabling informed decision-making for users.