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Objectives: To determine the severity of dental caries in South American Indigenous peoples., Methods: A systematic review was conducted regarding the severity of dental caries in South American Indigenous peoples using the following electronic databases: MEDLINE/PubMed, SCOPUS, SciELO, LILACS and grey literature up to March 2018. Literature search was conducted up to March 2018. No restrictions on language or year of publication were applied. Descriptive analysis and meta-analysis of studies were performed to determine mean dmft/DMFT index (decayed, missing and filled teeth) and temporal trends for selected age brackets., Results: The search strategy retrieved 698 studies, of which 70 full-text articles were assessed for eligibility and 28 were included in the qualitative analysis. Finally, 18 papers were included in the meta-analysis. Publication year ranged from 1964 to 2018. Mean dmft for 5-year-old children was 5.73 (95% CI 4.67-6.79), and mean DMFT for 12-year-olds was 3.14 (95% CI 1.88-4.40). Estimated DMFT for 15-19 years, 35-44 years and 65-74 years was 5.53 (95% CI 2.97-8.09), 19.41 (95% CI 11.88-26.93) and 28.19 (24.83-31.55), respectively. DMFT was higher than that reported in general population surveys in Brazil, Chile, Uruguay and Venezuela for all age brackets with available data. Heterogeneity was observed in all age brackets, ranging from 79.7 to 99.7%., Conclusion: Dental caries remains a significant public health problem for South American Indigenous peoples. Prevention and treatment strategies that consider cultural specificities are needed., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)