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RATIONALE: Electronic cigarettes (EC) are handheld electronic vaping devices that produce an aerosol by heating a liquid. People who smoke, healthcare providers, and regulators want to know if EC can help people quit smoking, and if they are safe to use for this purpose. This update was conducted as part of a living systematic review. OBJECTIVES: To examine the safety, tolerability, and effectiveness of EC for helping people who smoke tobacco achieve long-term smoking abstinence, in comparison to non-nicotine EC, other smoking cessation treatments, and no treatment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 January 2026, reference-checked, and contacted study authors. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) randomising people who smoked to an EC or control condition. Studies had to measure an eligible outcome. OUTCOMES: Critical outcomes were abstinence from smoking after at least six months, adverse events (AEs), and serious adverse events (SAEs). Important outcomes were biomarkers, toxicants/carcinogens, long-term study product use and long-term patterns of EC and combustible cigarette use. RISK OF BIAS: We used the RoB 1 tool to assess risk of bias for each study and GRADE to assess evidence certainty. SYNTHESIS METHODS: We followed standard Cochrane methods for screening and data extraction. Where appropriate, we pooled data using random-effects models to calculate risk ratios (RRs) with 95% confidence intervals (CI) for dichotomous outcomes apart from SAEs. For SAEs, we calculated risk differences (RD) and 95% CI. For continuous outcomes, we calculated mean differences (MD) or standardised mean differences (SMD) with 95% CIs. INCLUDED STUDIES: We included 80 completed RCTs, representing 29,861 participants. Nine of these RCTs were new to this update. We rated 12 included studies as being at low risk of bias, 41 at high risk, and the remainder at unclear risk overall. SYNTHESIS OF RESULTS: Nicotine EC result in increased quit rates compared to nicotine replacement therapy (NRT) (high-certainty evidence) (RR 1.61, 95% CI 1.23 to 2.12; I² = 55%; 11 studies, 4114 participants). In absolute terms, this might translate to an additional four quitters per 100 (95% CI 1 to 7 more). The proportion of participants experiencing AEs may be similar between groups (low-certainty evidence, limited by imprecision and inconsistency) (RR 0.95, 95% CI 0.72 to 1.24; I² = 72%; 8 studies, 3107 participants) and the proportion of participants experiencing SAEs is probably similar between groups (moderate-certainty evidence, limited by imprecision) (RD 0.01, 95% CI -0.01 to 0.02; I² = 0%; 10 studies, 4045 participants). Nicotine EC probably result in increased quit rates compared to non-nicotine EC (moderate-certainty evidence, limited by imprecision) (RR 1.34, 95% CI 1.05 to 1.69; I² = 0%; 7 studies, 1918 participants). In absolute terms, this might lead to an additional two quitters per 100 (95% CI 0 to 4 more). There is probably little to no difference in the proportion of participants experiencing AEs between these groups (moderate-certainty evidence, limited by imprecision) (RR 1.01, 95% CI 0.95 to 1.08; I² = 0%; 6 studies, 909 participants) and there may be similar proportions of SAEs (RD 0.00, 95% CI -0.01 to 0.01; I² = 0%; 11 studies, 1786 participants; low-certainty evidence downgraded due to very serious imprecision). Compared to behavioural support only or no support, quit rates may be higher for participants randomised to nicotine EC (low-certainty evidence due to risk of bias) (RR 1.75, 95% CI 1.39 to 2.20; I² = 13%; 11 studies, 7214 participants). In absolute terms, this represents an additional two quitters per 100 (95% CI 2 to 6 more). There was some evidence that people randomised to nicotine EC may be more likely to experience (non-serious) AEs (RR 1.22, 95% CI 1.00 to 1.49; I² = 58%; 11 studies, 2801 participants; very low-certainty evidence due to imprecision and risk of bias), but the evidence is uncertain. There was insufficient evidence to determine whether rates of SAEs differed between groups (RD 0.00, 95% CI -0.00 to 0.01; I² = 0%; 18 studies, 5032 participants; very low-certainty evidence downgraded due to imprecision and risk of bias). AUTHORS' CONCLUSIONS: There is high-certainty evidence that nicotine EC increase quit rates compared to NRT, and moderate-certainty evidence that they probably increase quit rates compared to EC without nicotine. Evidence comparing nicotine EC with behavioural support or no support also suggests benefit, but is less certain due to risk of bias inherent in the study designs. Overall incidence of SAEs was low across all study arms and there is now moderate-certainty evidence that SAE rates are similar when comparing nicotine EC with NRT. There was also no evidence of a difference in AEs between nicotine and non-nicotine EC nor between nicotine EC and NRT, but low-certainty evidence for increased AEs compared with behavioural support/no support. We did not detect evidence of serious short-term harm from nicotine EC, but longer, larger trials are needed to fully evaluate safety. The included studies tested regulated nicotine-containing EC; illicit products and/or products containing other active substances (e.g. tetrahydrocannabinol (THC)) may have different harm profiles. The main limitation of the evidence base remains imprecision for some comparisons. Further RCTs are underway. To ensure the review continues to provide up-to-date information, this is a living systematic review. We run and screen searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the most recent version of this review. FUNDING: Cancer Research UK (PICCTR-2024/100012). The addition of new outcomes relating to vaping and smoking at six months or more was supported by the National Cancer Institute of the National Institutes of Health (NIH) and FDA Center for Tobacco Products (CTP) under Award Number 2U54CA229974. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. The funders were not involved in the decision to submit for publication. REGISTRATION: Protocol (2012) available via DOI: 10.1002/14651858.CD010216 (updates to 2012 protocol available via https://osf.io/upgjc/overview.

BACKGROUND: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e-liquid. People who smoke report using ECs to stop or reduce smoking, but some organisations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This review is an update of a review first published in 2014. OBJECTIVES: To evaluate the effect and safety of using electronic cigarettes (ECs) to help people who smoke achieve long-term smoking abstinence. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO for relevant records to January 2020, together with reference-checking and contact with study authors. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and randomized cross-over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, AEs, and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta-analyses. MAIN RESULTS: We include 50 completed studies, representing 12,430 participants, of which 26 are RCTs. Thirty-five of the 50 included studies are new to this review update. Of the included studies, we rated four (all which contribute to our main comparisons) at low risk of bias overall, 37 at high risk overall (including the 24 non-randomized studies), and the remainder at unclear risk. There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low-certainty evidence (limited by very serious imprecision) of no difference in the rate of adverse events (AEs) (RR 0.98, 95% CI 0.80 to 1.19; I2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I2 = n/a; 2 studies, 727 participants). There was moderate-certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.71, 95% CI 1.00 to 2.92; I2 = 0%; 3 studies, 802 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 12). These trials used EC with relatively low nicotine delivery. There was low-certainty evidence, limited by very serious imprecision, that there was no difference in the rate of AEs between these groups (RR 1.00, 95% CI 0.73 to 1.36; I2 = 0%; 2 studies, 346 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.25, 95% CI 0.03 to 2.19; I2 = n/a; 4 studies, 494 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.50, 95% CI 1.24 to 5.04; I2 = 0%; 4 studies, 2312 participants). In absolute terms this represents an increase of six per 100 (95% CI 1 to 14). However, this finding was very low-certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs varied, but some evidence that non-serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.17, 95% CI 1.04 to 1.31; I2 = 28%; 3 studies, 516 participants; SAEs: RR 1.33, 95% CI 0.25 to 6.96; I2 = 17%; 5 studies, 842 participants). Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate over time with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the degree of effect, particularly when using modern EC products. Confidence intervals were wide for data on AEs, SAEs and other safety markers. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow-up was two years and the overall number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up-to-date information for decision-makers, this review is now a living systematic review. We will run searches monthly from December 2020, with the review updated as relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status.