Tuberculosis (TB) in older people is a significant public health problem in low TB-incidence countries. Older persons have increased TB incidence, higher reactivation and mortality. A delay in diagnosis and initiation of TB treatment in patients with atypical clinical and radiological features is a significant factor of widespread transmission. This study aimed to evaluate the cost-effectiveness of interferon-gamma release assays [IGRAs; QuantiFERON®-TB Gold In-Tube (QFT) and T-SPOT®.TB (T-SPOT)] compared to the tuberculin skin test (TST) and chest X-ray (CXR) examination for TB screening for nursing homes. Decision trees and Markov models were constructed using a societal perspective on a lifetime horizon. Seven strategies: no screening, TST, QFT, T-SPOT, TST followed by QFT, TST followed by T-SPOT, and CXR were considered. QFT [US$ 401·9, 4·36 707 QALY (year 2014 values)] was the most cost-effective at the willingness-to-pay level of US$ 50 000/QALY gained. TST followed by QFT was the most cost-effective in residents with comorbidities. CXR was less cost-effective. Cost-effectiveness was sensitive to latent TB infection (LTBI) rate and bacillus Calmette-Guérin vaccination rate. Effective LTBI screening using IGRA is recommended to prevent TB transmission not only in nursing homes but also in local communities in low-incidence countries.