Diagnosis of latent Mycobacterium tuberculosis infection (LTBI) by the tuberculin skin test (TST) is hampered due to anergy and impaired sensitivity in chronic renal failure (CRF) patients. We aimed to compare the diagnostic performance of the TST with that of interferon-gamma immunospot (T-SPOT.TB (R)) assay in diagnosing LTBI in CRF and immunocompetent (IC) patients. A total of 74 CRF and 75 IC patients prospectively underwent the TST and T-SPOT. TB. Latent M. tuberculosis infection estimated by TST and T-SPOT. TB was detected in 69% and 43 of CRF; 52 and 35% of IC patients, respectively. The sensitivity and specificity of the T-SPOT. TB were 73 and 74% in IC, whereas 50 and 55% in CRF patients. In conclusion, the prevalence of LTBI was noteworthy in both IC and CRF patients. T-SPOT. TB was less sensitive and specific than the IC group in CRF patients. Both T-SPOT. TB and TST were not associated with the TB exposure.