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Schistosomiasis is an important public health problem, with high morbidity and mortality in endemic countries. We analysed the epidemiological characteristics and time trends of schistosomiasis-related mortality in Brazil. We performed a nationwide study based on official mortality data obtained from the Brazilian Mortality Information System. We included all deaths in Brazil between 2000 and 2011, in which schistosomiasis was mentioned on the death certificate as an underlying or associated cause of death (multiple causes of death). We calculated crude and age-adjusted mortality rates (per 100,000 inhabitants), and proportional mortality rates. Trends over time were assessed using joinpoint regression models. Over the 12-year study period, 12,491,280 deaths were recorded in Brazil. Schistosomiasis was mentioned in 8,756 deaths, including in 6,319 (72.2%) as an underlying cause and in 2,437 (27.8%) as an associated cause. The average annual age-adjusted mortality rate was 0.49 deaths/100,000 inhabitants (95% confidence interval: 0.46–0.52) and proportional mortality rate was 0.070% (95% confidence interval: 0.069–0.072). Males (0.53 deaths/100,000 inhabitants), those aged ⩾70 years (3.41 deaths/100,000 inhabitants), those of brown race/colour (0.44 deaths/100,000 inhabitants), and residents in the Northeast region of Brazil (1.19 deaths/100,000 inhabitants) had the highest schistosomiasis-related death rates. Age-adjusted mortality rates showed a significant decrease at a national level (Annual Percent Change: −2.8%; 95% confidence interval: −4.2 to −2.4) during the studied period. We observed decreasing mortality rates in the Northeast (Annual Percent Change: −2.5%; 95% confidence interval: −4.2 to −0.8), Southeast (Annual Percent Change: −2.2%; 95% confidence interval: −3.6 to −0.9), and Central-West (Annual Percent Change: −7.9%; 95% confidence interval: −11.3 to −4.3) regions, while the rates remained stable in the North and South regions. Despite the reduced mortality, schistosomiasis is still a neglected cause of death in Brazil, with considerable regional differences. Sustainable control measures should focus on increased coverage, and intensified and tailored control measures, to prevent the occurrence of severe forms of schistosomiasis and associated deaths. [ABSTRACT FROM AUTHOR]