Background Emergency departments (EDs) offer a valuable opportunity to intervene to support people to quit smoking. We sought to determine the effectiveness of smoking cessation interventions delivered in the ED setting on rates of abstinence at the longest follow‐up. Methods We undertook a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines considering only randomised controlled trials (RCTs), based in the ED, where the goal of the intervention was smoking cessation and follow-up was at least 3 months. We systematically searched electronically published literature and trial registries from inception to May 2025. We pooled data using a Mantel-Haenszel randomeffects model for behavioural interventions without pharmacotherapy, and using a fixed-effects model for interventions incorporating nicotine replacement therapy (NRT), with results reported as risk ratios (RR) and 95% CIs. The primary outcome was smoking cessation using the strictest available measure, biochemically validated where possible. Risk of bias was assessed using the Cochrane risk of bias tool. Certainty of overall evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Results Nineteen RCTs met inclusion criteria, of which 17 were deemed suitable for incorporating into meta-analyses. Participants randomised to receive a smoking cessation intervention involving NRT in the ED were significantly more likely to achieve abstinence (RR 1.55, 95%CI 1.27 to 1.89, p<0.0001, 6 RCTs, n=3528, I2=46%). Trials involving behavioural support alone delivered in the ED had an RR of quitting compared with controls of 1.18 (95% CI 0.85 to 1.64, p=0.32, 11 RCTs, N=4711, I2=37%). Of the 17 studies included in the meta-analyses, 14 were at high risk of bias, 1 at low risk and 2 where the risk was unclear. One study incorporated e-cigarettes and was not incorporated in the meta-analysis but demonstrated evidence of effectiveness. Conclusion There is moderate certainty evidence that smoking cessation interventions incorporating pharmacotherapy delivered in the ED are effective in supporting smoking cessation.