Previous health impact assessments of temperature-related mortality in Europe indicated that the mortality burden attributable to cold is much larger than for heat. Questions remain as to whether climate change can result in a net decrease in temperature-related mortality. In this study, we estimated how climate change could affect future heat-related and cold-related mortality in 854 European urban areas, under several climate, demographic and adaptation scenarios. We showed that, with no adaptation to heat, the increase in heat-related deaths consistently exceeds any decrease in cold-related deaths across all considered scenarios in Europe. Under the lowest mitigation and adaptation scenario (SSP3-7.0), we estimate a net death burden due to climate change increasing by 49.9% and cumulating 2,345,410 (95% confidence interval = 327,603 to 4,775,853) climate change-related deaths between 2015 and 2099. This net effect would remain positive even under high adaptation scenarios, whereby a risk attenuation of 50% is still insufficient to reverse the trend under SSP3-7.0. Regional differences suggest a slight net decrease of death rates in Northern European countries but high vulnerability of the Mediterranean region and Eastern Europe areas. Unless strong mitigation and adaptation measures are implemented, most European cities should experience an increase of their temperature-related mortality burden.