Objective: Pulmonary involvement is common in patients with systemic sclerosis (SSc), and this condition causes substantial morbidity and mortality. Disrupted immunity from the disease or associated medication may render such patients subject to tuberculosis (TB) infection. However, the relationship between SSc and TB has not yet been investigated. Methods: Using the Taiwan National Health Insurance Research Database, 838 patients with SSc diagnosed in Taiwan during 2000-2006 were identified and followed for emergence of TB infection. Incidence rate ratios (IRR) of TB compared to 8380 randomly selected age-, sex-, and comorbiditymatched controls without SSc were calculated. The Cox proportional hazards model was used for multivariate adjustment to identify independent risk factors for TB infection. Results: The risk of TB infection was higher in the SSc cohort than in controls (IRR 2.81, 95% CI 1.36-5.37; p = 0.004), particularly for pulmonary TB (IRR 2.53, 95% CI 1.08-5.30; p = 0.022). Other independent risk factors for TB infection in patients with SSc were age =≥ 60 years [hazard ratio (HR) 3.52, 95% CI 1.10-11.33; p = 0.035] and pulmonary hypertension (PH; HR 6.06, 95% CI 1.59-23.17; p = 0.008). Mortality did not differ for SSc patients with or without TB. Conclusion: In this nationwide study, the incidence of TB infection was significantly higher among patients with SSc than in controls without SSc. Special care should be taken in managing patients with SSc who are at high risk for TB, especially those aged = 60 years or who also have PH.