AbstractThroughout Europe, computed tomography (CT) screening for lung cancer is in a phase of clinical implementation or reimbursement evaluation. To efficiently select individuals for screening, the use of lung cancer risk models has been suggested, but their incremental (cost‐)effectiveness relative to eligibility based on pack‐year criteria has not been thoroughly evaluated for a European setting. We evaluate the cost‐effectiveness of pack‐year and risk‐based screening (PLCOm2012 model‐based) strategies for Switzerland, which aided in informing the recommendations of the Swiss Cancer Screening Committee (CSC). We use the MISCAN (MIcrosimulation SCreening ANalysis)‐Lung model to estimate benefits and harms of screening among individuals born 1940 to 1979 in Switzerland. We evaluate 1512 strategies, differing in the age ranges employed for screening, the screening interval and the strictness of the smoking requirements. We estimate risk‐based strategies to be more cost‐effective than pack‐year‐based screening strategies. The most efficient strategy compliant with CSC recommendations is biennial screening for ever‐smokers aged 55 to 80 with a 1.6% PLCOm2012 risk. Relative to no screening this strategy is estimated to reduce lung cancer mortality by 11.0%, with estimated costs per Quality‐Adjusted Life‐Year (QALY) gained of €19 341, and a €1.990 billion 15‐year budget impact. Biennial screening ages 55 to 80 for those with 20 pack‐years shows a lower mortality reduction (10.5%) and higher cost per QALY gained (€20 869). Despite model uncertainties, our estimates suggest there may be cost‐effective screening policies for Switzerland. Risk‐based biennial screening ages 55 to 80 for those with ≥1.6% PLCOm2012 risk conforms to CSC recommendations and is estimated to be more efficient than pack‐year‐based alternatives.