The optimal means for detecting and managing liver transplantation (LT) patients with latent tuberculosis (TB) are not well defined. Our study aims were to (1) determine the frequency and risk factors of latent TB in a large cohort of consecutive adult LT candidates and (2) determine the safety and efficacy of isoniazid treatment in LT recipients with latent TB. A review of patients assessed for latent TB by skin testing using purified protein derivative (PPD; January 2004 to September 2008) or with the interferon-c release assay QuantiFERON-TB Gold (QFT; March 2008 to October 2009) was undertaken. The baseline clinical features and outcomes of subjects with latent TB and subjects without latent TB were compared. Twentyfive of 420 subjects (6.0%) were positive for PPD. In comparison, 11 of 119 subjects (9.2%) had a positive QFT assay, and 15 others (13%) had indeterminate results. Both PPD-positive and QFT-positive subjects were less likely to be Caucasian than subjects without latent TB (p < 0.001). The 3-year survival rate of the 25 LT recipients with latent TB was similar to that of the 296 LT recipients without latent TB (78.7% versus 74.6%, P ΒΌ 0.58). Fifteen of the 25 latent TB patients received isoniazid at a mean of 0.67 months after LT. Although isoniazid was discontinued in 8 subjects because of possible side effects, none of the 25 latent TB patients developed TB reactivation after transplantation with a mean follow-up of 33 months. In conclusion, both QFT testing and PPD testing demonstrate similar rates of detecting latent TB infection in American LT candidates, but QFT testing also leads to a moderate rate of indeterminate test results. Early isoniazid chemoprophylaxis after LT is poorly tolerated and is frequently discontinued.