BackgroundA national, lung cancer screening programme is under consideration in Australia, and we assessed cost-effectiveness using updated data and assumptions.MethodsWe estimated the cost-effectiveness of lung screening by applying screening parameters and outcomes from either the National Lung Screening Trial (NLST) or the NEderlands–Leuvens Longkanker Screenings ONderzoek (NELSON) to Australian data on lung cancer risk, mortality, health-system costs, and smoking trends using a deterministic, multi-cohort model. Incremental cost-effectiveness ratios (ICERs) were calculated for a lifetime horizon.ResultsThe ICER for lung screening compared to usual care in the NELSON-based scenario was AU$39,250 (95% CI $18,150–108,300) per quality-adjusted life year (QALY); lower than the NLST-based estimate (ICER = $76,300, 95% CI $41,750–236,500). In probabilistic sensitivity analyses, lung screening was cost-effective in 15%/60% of NELSON-like simulations, assuming a willingness-to-pay threshold of $30,000/$50,000 per QALY, respectively, compared to 0.5%/6.7% for the NLST. ICERs were most sensitive to assumptions regarding the screening-related lung cancer mortality benefit and duration of benefit over time. The cost of screening had a larger impact on ICERs than the cost of treatment, even after quadrupling the 2006–2016 healthcare costs of stage IV lung cancer.DiscussionLung screening could be cost-effective in Australia, contingent on translating trial-like lung cancer mortality benefits to the clinic.