Lung cancer (LC) has the highest cancer mortality worldwide with poor prognosis. Screening with low-dose computed tomography (LDCT) in populations highly exposed to tobacco has been proposed to improve LC prognosis. Our objective was to perform a systematic review and meta-analysis to evaluate the efficacy of screening by LDCT compared with any other intervention in populations who reported tobacco consumption for more than 15 years on LC and overall mortality.Methods: We searched randomised controlled trials (RCTs) studying screening by LDCT compared with any other intervention in a population who reported an average smoking history greater than 15 pack-years from inception until the 19th February 2018 using Medline and Cochrane Library databases. Publication selection and data extraction were made independently by two double-blind reviewers.Results: Seven RCTs were included in the meta-analysis which corresponds to 84,558 participants. A significant relative reduction of LC-specific mortality of 17% (risk ratio [RR] = 0.83, 95% confidence interval [CI]: 0.76-0.91) and a relative reduction of overall mortality of 4% (RR = 0.96, 95% CI: 0.92-1.00) was observed in the screening group compared with the control group.Conclusion: In populations highly exposed to tobacco, screening by LDCT reduces lung cancer mortality.