Background <p>Chronic obstructive pulmonary disease (COPD) is frequently undiagnosed among ever-smokers. We evaluated the cost-effectiveness of targeted COPD case-finding using the PUMA questionnaire followed by spirometry among ever-smokers aged 50 years and older in Singapore.</p> Methods <p>A cohort Markov model compared two strategies: PUMA-based case-finding (PUMA score ≥4) followed by spirometry versus no case-finding, over a lifetime horizon from the healthcare payer perspective, with 3% annual discounting. A willingness-to-pay threshold of SGD75,000/QALY was applied.</p> Results <p>Case-finding yielded an incremental cost of SGD 2,475 and an incremental gain of 0.0339 QALYs per person (ICER: SGD 73,065/QALY). Probabilistic sensitivity analysis indicated a 71.1% probability of being cost-effective at SGD 75,000/QALY. The ICER was most sensitive to the odds ratio of exacerbation for individuals with mild and moderate COPD treated with Long-Acting Muscarinic Antagonist (LAMA), and the severity distribution of undiagnosed COPD.</p> Conclusions <p>PUMA-based targeted COPD case-finding followed by spirometry is likely to be cost-effective at Singapore’s willingness-to-pay threshold.</p>