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Background: Targeting low-dose computed tomography (LDCT) for lung cancer screening to persons at highest risk for lung cancer mortality has been suggested to improve screening efficiency. Objective: To quantify the value of risk-targeted selection for lung cancer screening compared with National Lung Screening Trial (NLST) eligibility criteria. Design: Cost-effectiveness analysis using a multistate prediction model. Data Sources: NLST. Target Population: Current and former smokers eligible for lung cancer screening. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Risk-targeted versus NLST-based screening. Outcome Measures: Incremental 7-year mortality, life expectancy, quality-adjusted life-years (QALYs), costs, and cost-effectiveness of screening with LDCT versus chest radiography at each decile of lung cancer mortality risk. Results of Base-Case Analysis: Participants at greater risk …