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Background Lung cancer (LC) is the most common cause of cancer death in the UK and worldwide, but screening with low-dose CT (LDCT) reduces LC deaths. The UK National Screening Committee has recommended nationwide roll-out of LDCT screening, but the optimal risk thresholds for eligibility remain uncertain.Methods We conducted a cost-effectiveness analysis in the Yorkshire Lung Screening Trial (YLST) population comparing three eligibility criteria: US Preventive Services Task Force (USPSTF) 2013, Prostate Lung Colorectal and Ovarian study (PLCO)M2012 ≥1.51% and Liverpool Lung Project model (LLP)v2 ≥5%. A Markov model estimated a no-screening counterfactual. Scenario analyses assessed how increasing PLCOM2012 (1.51%–7%) and LLPv2 (5%–9%) thresholds affected LC detection, costs and quality-adjusted life years (QALYs). Payouts per detected LC were calculated using mortality and utility estimates from the literature and cost data from the trial.Results Incremental cost-effectiveness ratios (ICERs) versus no screening were £3949 (USPSTF 2013), £3797 (LLPv2≥5%) and £4013 (PLCOM2012≥1.51%). PLCOM2012 yielded the largest numbers screened and LCs detected, most QALYs gained and highest incremental net monetary benefit. Raising LLPv2 and PLCOM2012 thresholds reduced both ICERs and QALYs gained.Conclusion All three screening eligibility criteria are cost-effective according to the UK’s willingness to pay threshold of £20 000/QALY. Within the range of thresholds observed in YLST, PLCO M2012 thresholds between ≥1.51% and ≥4% offered the most efficient cost–benefit trade-offs. Evidence suggests that lowering thresholds further would detect more LC cases while remaining cost-effective. These findings support the criteria implemented in YLST, but do not by themselves identify the optimal screening threshold for the wider UK population.Trial registration number ISRCTN42704678.