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Objectives: To evaluate the impact of immigration on tuberculosis (TB)-HIV co-infection in Spain in a prospective cohort of HIV patients., Methods: Among 7761 HIV patients, we evaluated 1284 with at least one episode of TB between 1987 and 2006. Variables were compared between immigrants and Spaniards., Results: Incidence of TB decreased from 20 to five cases per 100 patient-years in 2006 (P<0.01) and was always higher in immigrants than in Spaniards. The proportion of immigrants increased, reaching almost 50% of both new cases of HIV and TB-HIV co-infection in 2006. In 34.4% of patients, TB and HIV infection were diagnosed within the same year; simultaneous diagnosis was more frequent in immigrants (83.3%vs. 16.7%, P<0.001). Mortality was associated independently with age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05], TB diagnosis before 1996 (HR 2.6, 95% CI 1.8-3.6), use of highly active antiretroviral treatment (HR 0.494, 95% CI 0.37-0.66) and CD4 cell count at TB diagnosis (HR 0.996, 95% CI 0.995-0.997)., Conclusions: Immigrants have a major impact on the incidence of TB in HIV patients, slowing down the decreasing trend in Spain. Simultaneous diagnosis of the co-infection in immigrants reveals a need to intensify HIV case finding in immigrants in Spain.