SETTING Tuberculosis (TB) referral clinic in Vancouver, British Columbia, Canada. BACKGROUND Screening for and treatment of latent TB infection (LTBI) in at-risk populations are the cornerstone of TB control in low-incidence countries. Persons at low risk often undergo the tuberculin skin test (TST) for reasons other than contact. Little information exists on the actual risk of TB in this population. OBJECTIVE To determine the risk of TB in screened subjects without known risk factors. DESIGN Retrospective descriptive analysis of demographics, TST reaction size and TB disease occurrence in 98333 low-risk subjects screened from 1990 to 2002. RESULTS The average annual disease rate was 0.4 per 100000 population (cumulative rate 7.4/100000) from 1990 to 2006, and TB was diagnosed only in the foreign-born. Risk of TB in the foreign-born increased with larger TST reaction size (P < 0.03). Completion of treatment for LTBI was not documented for any of the subsequent active TB cases. CONCLUSION In a low-risk screened population, active TB disease was found only in the foreign-born. Treatment of LTBI is not recommended in persons with a positive TST and no additional risk factors. Local screening programs should focus on populations with confirmed risk factors for disease.