OBJECTIVES: This study attempted to estimate the cost-effectiveness of implementing computed tomography (CT) screening based on the experience of the National Lung Screening Trial (NLST) for early diagnosis of lung cancer in Taiwan.  METHODS: From a nation-wide, 13-year follow-up cohort, we estimated quality-adjusted life expectancy (QALE), loss-of-QALE, and lifetime healthcare expenditures per case of lung cancer stratified by pathology and stage. Stage distributions for CT-screening and no-screening were assumed equal to those of the NLST to estimate the savings in loss-of-QALE and additional costs of lifetime healthcare expenditures after CT screening. Costs attributable to false-positive cases and radiation-induced lung cancer were added for comparison. RESULTS: The incremental costs were US$22,755 per person. After dividing it by savings of loss-of-QALE (1.16 quality-adjusted life year (QALY)), the incremental cost-effectiveness ratio (ICER) was US$19,683 per QALY. The ICER rose to US$31,066 per QALY and US$29,349 per QALY, respectively, when cost of CT and numbers of diagnostic follow-ups doubled. If we applied the stage distribution of Taiwan without regular chest radiography as the non-screened group, ICER became US$11,367 per QALY. CONCLUSIONS: Low-dose CT screening for early diagnosis of lung cancer in Taiwan would be cost-effective. This methodology provides a quasi-real world analysis from the payer’s perspective and could be applied for examining the cost-effectiveness of other screening programs.