© 2018 Achebak et al. http://creativecommons.org/licenses/by/4.0/. Background: Anthropogenic greenhouse gas emissions have increased summer temperatures in Spain by nearly one degree Celsius on average between 1980 and 2015. However, little is known about the extent to which the association between heat and human mortality has been modified. We here investigate whether the observed warming has been associated with an upward trend in excess mortality attributable to heat or, on the contrary, a decrease in the vulnerability to heat has contributed to a reduction of the mortality burden. Methods and findings: We analysed a dataset from 47 major cities in Spain for the summer months between 1980 and 2015, which included daily temperatures and 554,491 deaths from circulatory and respiratory causes, by sex. We applied standard quasi-Poisson regression models, controlling for seasonality and long-term trends, and estimated the temporal variation in heat-related mortality with time-varying distributed lag nonlinear models (DLNMs). Results pointed to a reduction in the relative risks of cause-specific and cause-sex mortality across the whole range of summer temperatures. These reductions in turn explained the observed downward trends in heat-attributable deaths, with the only exceptions of respiratory diseases for women and both sexes together. The heat-attributable deaths were consistently higher in women than in men for both circulatory and respiratory causes. The main limitation of our study is that we were not able to account for air pollution in the models because of data unavailability. Conclusions: Despite the summer warming observed in Spain between 1980 and 2015, the decline in the vulnerability of the population has contributed to a general downward trend in overall heat-attributable mortality. This reduction occurred in parallel with a decline in the vulnerability difference between men and women for circulatory and cardiorespiratory mortality. Despite these advances, the risk of death remained high for respiratory diseases, and particularly in women.