Health care workers (HCW’s) are always at an increased risk of contracting tuberculosis (TB) infection. In Saudi Arabia, Interferon Gamma Release Assay (IGRA) has not been evaluated as a screening tool for latent TB infection (LTBI) among HCW’s considering their high demographic diversity. During February 2012 to January 2015 a cross sectional study has been conducted in a tertiary care center with maximum demographically diverse staff population in the capital city-Riyadh. After a short interview and consenting, all the candidates were subjected to tuberculin skin test (TST) and QuantiFERON TB gold In-tube test (QFT). A logistic regression analysis was carried out for establishing the associations between putative risk factors and the diagnostic tests. The candidates were classified according to geographical origin and a detailed analysis was conducted on the impact of their origin towards the results of TST and QFT. Of the 1595 candidates enrolled, 90.6% were BCG vaccinated, female (67.9%) and mainly nurses (53.2%). Candidates with high risk of suspected or confirmed TB patient exposure were 56.1% and 76.5% of them had <10 year’s work experience. TST positivity was observed in 503 (31.5%) candidates, while QFT was positive among 399 (25%). Majority of the candidates were non-Saudi (83%) and predominantly (52.4%) from Western Pacific region. Concordant results were obtained in 14.2% of positive cases and 57.7% negative cases. The disagreements between the two tests were relatively high (kappa co-efficient-0.312±0.026, p value- <0.00001) as TST positive/QFT negative discordance was 54.8% while TST negative/QFT positive discordance was 15.7%. Age of the candidates, BCG vaccination, and South East Asian origin were associated with TST positivity while Occupational TB exposure and geographical origin of the candidates were associated with QFT positivity. A regular follow up on recently TST converted candidates showed no progression to active TB. The putative factors associated with the discordance were origin of the candidate (p value <0.001), profession (p value-0.001), BCG vaccination (p value-0.001) and occupational TB exposure level (P value-0.001). The study demonstrated high level prevalence of LTBI among the demographically diverse study candidates. The agreement between QFT and TST was poor, thus QFT alone cannot be recommended in our setting for a routine LTBI screening. Origin of the candidates has strong association with the results of TST and QFT. The discordant results particularly TST negative and QFT positive needs more detailed analysis.