Abstract Background: The objective of this study was to assess the prevalence of latent tuberculosis infection (LTBI) in risk groups in Krakow, using the QuantiFERON-TB Gold In-Tube (QFT-GIT) test and the tuberculin skin test (TST); we also sought to assess the rate of progression to active disease over 4-5 y of follow-up. Methods: QFT-GIT tests were performed on 785 subjects and the TST on 701 subjects from the risk groups of homeless persons, close contacts, periodic contacts, and residents of long-term care facilities (LTCFs), and subjects from a low risk group. Results: In homeless persons, close contacts, periodic contacts, LTCF residents, and low risk persons, a positive QFT-GIT was found in 36.7%, 27.2%, 27.0%, 21.1%, and 23.7% of subjects, respectively, while a positive TST was found in 55.8%, 47.4%, 47.6%, 43.2%, and 47.9%, respectively. Of 63 homeless subjects, 5 developed active TB over 248 person-y of follow-up (incidence rate (IR) 20 per 1000 person-y, 95% confidence interval (CI) 8.4-48.5); of 148 close contacts, 5 developed active TB over 740 person-y of follow-up (IR 7, 95% CI 2.8-16.2); of 145 periodic contacts, 2 developed active TB over 580 person-y of follow-up (IR 4, 95% CI 0.9-13.8). The IR per 1000 person-y (95% CI) among subjects with a positive QFT-GIT was 30 (9.0-86.1) for homeless subjects, 18 (5.7-54.7) for close contacts, and 13 (3.2-51.3) for periodic contacts. In Poland there is no policy for the provision of LTBI treatment to people with a positive QFT or TST; therefore, the estimated rates of disease progression were analysed amongst untreated subjects. Conclusions: The prevalence of positive QFT-GIT and TST was high in the study risk groups. The best predictor of active TB in the homeless and close contacts groups was a positive QFT-GIT together with a positive TST.