A cohort of 42,655 clients that were first registered with the Elderly Health Service in 2000 were followed prospectively through the tuberculosis (TB) notification registry until the end of 2002. A total of 286 active TB cases (186 culture confirmed) were identified. The annual TB notification rates were 735, 427, and 174 per 100,000 among current smokers, ex-smokers, and never-smokers, respectively (p < 0.001). The trend in TB risk persisted after the control of background characteristics using Cox proportional hazards analysis (adjusted hazard ratios [HRs]: 2.63, 1.41, and 1, p < 0.001). In comparison with never-smokers, current smokers had an excess risk of pulmonary TB (adjusted HR, 2.87; 95% confidence interval [CI], 2.00-4.11; p < 0.001), but not extrapulmonary TB (adjusted HR, 1.04; 95% CI, 0.33-3.30; p = 0.95). Among the current smokers, those who developed TB smoked more cigarettes per day than those who did not (13.43, SD 8.76 vs. 10.96, SD 7.87, p = 0.01). A statistically significant dose-response relationship was observed with respect to active TB and culture-confirmed TB (both p < 0.05). Smoking accounted for 32.8% (95% CI, 14.9-48.0%), 8.6% (95% CI, 3.3-15.1%), and 18.7% (95% CI, 7.7-30.4%) of the TB risk among males, females, and the entire cohort, respectively. Approximately 44.9% (95% CI, 20.7-64.6%) of the sex difference was attributable to smoking.