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There is an urgent need for more information about the climate change impact on health in order to strengthen the commitment to tackle climate change. However, few studies have quantified the health impact of climate change in Brazil and in the Latin America region. In this paper, we projected the impacts of temperature on cardiovascular (CVD) mortality according to two climate change scenarios and two regionalized climate model simulations in Brazilian cities. We estimated the temperature-CVD mortality relationship in 21 Brazilian cities, using distributed lag non-linear models in a two-stage time-series analysis. We combined the observed exposure-response functions with the daily temperature projected under two representative concentration pathways (RCP), RCP8.5 and RCP4.5, and two regionalized climate model simulations, Eta-HadGEM2-ES and Eta-MIROC5. We observed a trend of reduction in mortality related to low temperatures and a trend of increase in mortality related to high temperatures, according to all the investigated models and scenarios. In most places, the increase in mortality related to high temperatures outweighed the reduction in mortality related to low temperatures, causing a net increase in the excess temperature-related mortality. These trends were steeper according to the higher emission scenario, RCP8.5, and to the Eta-HadGEM2-ES model. According to RCP8.5, our projections suggested that the temperature-related mortality fractions in 2090-99 compared to 2010–2019 would increase by 8.6% and 1.7%, under Eta-HadGEM2-ES and Eta-MIROC5, respectively. According to RCP4.5, these values would be 0.7% and −0.6%. For the same climate model, we observed a greater increase trend in temperature-CVD mortality according to RCP8.5, highlighting a greater health impact associated with the higher emission scenario. Our results may be useful to support public policies and strategies for mitigation of and adaptation to climate change, particularly in the health sector. • We estimated climate change impacts on temperature-CVD mortality in Brazil. • The projections showed a reduction in CVD mortality related to low temperatures. • The projections showed an increase in CVD mortality related to high temperatures. • We found a net increase in temperature-related mortality in most cities. • A greater health impact was associated with the higher emission scenario. [ABSTRACT FROM AUTHOR]