COPD is a highly underdiagnosed disease; however, due to the lack of treatment options for patients with mild disease, the benefits of early detection remain unclear. Previous studies have shown that systematic and opportunistic case finding strategies in primary care settings are effective at detecting new cases of COPD, but their long-term cost-effectiveness remains unclear. We evaluated a wide range of case detection strategies that included different eligibility criteria, case detection method, and period of intervention. We found that regular administration of questionnaire-based assessments of COPD risk during the routine primary care visits of all patients ≥40 years is a cost-effective approach to early detection. Our results provide an important message for health policymakers and clinicans: early detection strategies for COPD are cost-effective, and patients with risk factors for COPD should receive case detection regularly.