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Background: The prevalence of respiratory symptoms and confirmed tuberculosis (TB) among indigenous groups in Paraguay is unknown., Methods: This study assessed the prevalence of respiratory symptoms, confirmed pulmonary TB, and associated socio-economic factors among indigenous Paraguayan populations. Indigenous persons residing in selected communities were included in the study. A total of 24,352 participants were interviewed at home between October and December 2012. Respiratory symptomatic individuals were defined as those with respiratory symptoms of TB. A hierarchical Poisson regression analysis was performed with four levels: individual characteristics, living conditions and environmental characteristics, source of food, and type of nutrition., Findings: In this study, 1,383 participants had respiratory symptoms (5.7%), but only 10 had culture-confirmed TB (41/100,000 inhabitants). The small number of cases did not allow evaluation of the risk factors for TB. Age older than 37 years was associated with a two-fold increased risk of symptoms. Female sex; family history of TB; type of housing; home heating; a lack of hunting, fishing, or purchasing food; and a lack of vegetable consumption were also associated with the presence of symptoms. A lack of cereal consumption had a protective effect. Members of the Ayoreo or Manjui ethnic groups had a three-fold increased risk of symptoms., Main Conclusion: Individual characteristics, dietary habits, and belonging to specific ethnic groups were associated with respiratory symptoms.