Tuberculosis infection represents a global health problem and a great risk to health care workers. The detection and treatment of latent tuberculosis infection is a key strategy in the control of tuberculosis. The aim of this study was to estimate the usefulness of QuantiFERON-TB Gold In-Tube test which is an interferon-gamma release assay for the detection of latent tuberculosis infection, in a group of Egyptian Health Care Workers in comparison to the tuberculin skin test. A total of 100 Health Care Workers were enrolled. Subjects diagnosed as latent tuberculosis infection by tuberculin were 88% as compared to 36% by quantiferon. Higher tuberculin positive results were associated with direct contact to tuberculosis patients and job categories as physicians and nurses, while higher quantiferon positive results were associated with longer duration of employment and absence of BCG vaccination. The overall agreement between the two tests was poor (k=0.109). The negative discordant results (quantiferon negative/tuberculin positive) were 53% and were found among both contacts and non contact group, which could reflect high number of false positive tuberculin skin test. These data suggest that using IFN-γ method to screen new entrant health care workers for latent tuberculosis infection in our population could be more helpful because it is more specific for detecting latent tuberculosis infection compared to tuberculin skin test.