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Background: Neglected Tropical Diseases (NTDs) are important causes of morbidity, disability, and mortality among poor and vulnerable populations in several countries worldwide, including Brazil. We present the burden of NTDs in Brazil from 1990 to 2016 based on findings from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016). Methodology: We extracted data from GBD 2016 to assess years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for NTDs by sex, age group, causes, and Brazilian states, from 1990 to 2016. We included all NTDs that were part of the priority list of the World Health Organization (WHO) in 2016 and that are endemic/autochthonous in Brazil. YLDs were calculated by multiplying the prevalence of sequelae multiplied by its disability weight. YLLs were estimated by multiplying each death by the reference life expectancy at each age. DALYs were computed as the sum of YLDs and YLLs. Principal findings: In 2016, there were 475,410 DALYs (95% uncertainty interval [UI]: 337,334–679,482; age-standardized rate of 232.0 DALYs/100,000 population) from the 12 selected NTDs, accounting for 0.8% of national all-cause DALYs. Chagas disease was the leading cause of DALYs among all NTDs, followed by schistosomiasis and dengue. The sex-age-specific NTD burden was higher among males and in the youngest and eldest (children <1 year and those aged ≥70 years). The highest age-standardized DALY rates due to all NTDs combined at the state level were observed in Goiás (614.4 DALYs/100,000), Minas Gerais (433.7 DALYs/100,000), and Distrito Federal (430.0 DALYs/100,000). Between 1990 and 2016, the national age-standardized DALY rates from all NTDs decreased by 45.7%, with different patterns among NTD causes and Brazilian states. Most NTDs decreased in the period, with more pronounced reduction in DALY rates for onchocerciasis, lymphatic filariasis, and rabies. By contrast, age-standardized DALY rates due to dengue, visceral leishmaniasis, and trichuriasis increased substantially. Age-standardized DALY rates decreased for most Brazilian states, increasing only in the states of Amapá, Ceará, Rio Grande do Norte, and Sergipe. Conclusions/Significance: GBD 2016 findings show that, despite the reduction in disease burden, NTDs are still important and preventable causes of disability and premature death in Brazil. The data call for renewed and comprehensive efforts to control and prevent the NTD burden in Brazil through evidence-informed and efficient and affordable interventions. Multi-sectoral and integrated control and surveillance measures should be prioritized, considering the population groups and geographic areas with the greatest morbidity, disability, and most premature deaths due to NTDs in the country. [ABSTRACT FROM AUTHOR]