RATIONALE: There is limited guidance on the best ways to stop using nicotine-containing vapes (otherwise known as e-cigarettes) and ensure long-term abstinence, whilst minimising the risk of tobacco smoking and other unintended consequences. Treatments could include pharmacological interventions, behavioural interventions, or both. OBJECTIVES: To conduct a living systematic review assessing the benefits and harms of interventions to help people stop vaping compared to each other or to placebo or no intervention. To also assess how these interventions affect the use of combustible tobacco, and whether the effects vary based on participant characteristics. SEARCH METHODS: We searched the following databases from 1 January 2004 to 24 April 2024: CENTRAL; MEDLINE; Embase; PsycINFO; ClinicalTrials.gov (through CENTRAL); World Health Organization International Clinical Trials Registry Platform (through CENTRAL). We also searched the references of eligible studies and abstracts from the Society for Research on Nicotine and Tobacco 2024 conference, and contacted study authors. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) recruiting people of any age using nicotine-containing vapes, regardless of tobacco smoking status. Studies had to test an intervention designed to support people to quit vaping, and plan to measure at least one of our outcomes. OUTCOMES: Critical outcomes: vaping cessation; change in combustible tobacco use at six months or longer; number of participants reporting serious adverse events (SAEs) at one week or longer. RISK OF BIAS: We used the Cochrane RoB 1 tool to assess bias in the included studies. SYNTHESIS METHODS: We followed standard Cochrane methods for screening and data extraction. We grouped studies by comparisons and outcomes reported, and calculated individual study and pooled effects, as appropriate. We used random-effects Mantel-Haenszel methods to calculate risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. We used random-effects inverse variance methods to calculate mean differences and 95% CI for continuous outcomes. We assessed the certainty of the evidence using the GRADE approach. INCLUDED STUDIES: Nine RCTs, representing 5209 participants motivated to stop using nicotine-containing vapes at baseline, are included. In six studies, participants were abstinent from smoking tobacco cigarettes at baseline, although most studies included some participants who had previously smoked. Eight studies included participants aged 18 or older, three included only young adults (18 to 24 years), and one included 13- to 17-year-olds only. We judged three studies at low risk, three at high risk, and three at unclear risk of bias. SYNTHESIS OF RESULTS: Pharmacological interventions for quitting nicotine vaping Studies assessed combination nicotine replacement therapy (NRT), cytisine, and varenicline as pharmacological interventions for quitting vaping in comparison to placebo or no/minimal support (control). The point estimate for combination NRT indicated possible benefit, but the CI incorporated the possibility of no benefit and a potential benefit of control (very low-certainty evidence due to imprecision and risk of bias; RR 2.57, 95% CI 0.29 to 22.93; 1 study, 16 participants). The one study investigating cytisine did not report vaping cessation rates at six months or longer. Varenicline increased vaping cessation rates at six months, but the evidence was low certainty due to imprecision (RR 2.00, 95% CI 1.09 to 3.68; 1 study, 140 participants). Zero participants reported SAEs in the studies of combination NRT versus no/minimal support (1 study, 508 participants; low-certainty evidence due to imprecision) and cytisine versus placebo (1 study, 159 participants; low-certainty evidence due to imprecision). Three studies investigating varenicline measured the number of participants reporting SAEs. However, only one study reported an SAE (in the intervention arm); therefore, the effect estimate was calculated based on that single study (RR 2.60, 95% CI 0.11 to 62.16; 95 participants; low-certainty evidence due to imprecision). Behavioural interventions for quitting nicotine vaping Studies assessed reducing nicotine concentration and vaping behaviour (1 study) and text message-based interventions (3 studies) as behavioural interventions for stopping vaping in comparison to no/minimal support (control). In one study, the point estimate suggested nicotine/vaping reduction increased vaping cessation compared to minimal support at six-month follow-up, but the CI incorporated the possibility of no intervention effect and higher cessation rates in the control arm (RR 3.38, 95% CI 0.43 to 26.30; 17 participants; very low-certainty due to imprecision and risk of bias). There was low-certainty evidence (downgraded two levels due to indirectness) that text message-based interventions may have increased vaping cessation rates compared to control in 13- to 24-year-olds (RR 1.32, 95% CI 1.19 to 1.47; I = 0%; 2 studies, 4091 participants). The one study investigating nicotine/vaping behaviour reduction did not report on SAEs. One of the studies investigating text message-based interventions did report on SAEs; however, zero events were reported in both study arms (508 participants; low-certainty evidence due to imprecision). No studies reported change in combustible tobacco smoking at six-month follow-up or longer. AUTHORS' CONCLUSIONS: There is low-certainty evidence that text message-based interventions designed to help people stop nicotine vaping may help more youth and young adults to successfully stop than no/minimal support, and low-certainty evidence that varenicline may also help people quit vaping. Data exploring the effectiveness of combination NRT, cytisine, and nicotine/vaping behaviour reduction are inconclusive due to risk of bias and imprecision. Most studies that measured SAEs reported none; however, more data are needed to draw clear conclusions. Of note, data from studies investigating these interventions for quitting smoking have not demonstrated serious concerns about SAEs. No studies assessed the change in combustible tobacco smoking, including relapse to or uptake of tobacco smoking, at six-month follow-up or longer. It is important that future studies measure this so the complete risk profile of relevant interventions can be considered. We identified 20 ongoing RCTs. Their incorporation into the evidence base and the continued identification of new studies is imperative to inform clinical and policy guidance on the best ways to stop vaping. Therefore, we will continue to update this review as a living systematic review by running searches monthly and updating the review when relevant new evidence that will strengthen or change our conclusions emerges. FUNDING: Cancer Research UK (PRCPJT-Nov22/100012). National Institute of Health Research (NIHR206123) REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD016058.