BACKGROUND: Climate change can directly affect human health by varying exposure to non-optimal outdoor temperature. However, evidence on this direct impact at a global scale is limited, mainly due to issues in modelling and projecting complex and highly heterogeneous epidemiological relationships across different populations and climates. METHODS: We collected observed daily time series of mean temperature and mortality counts for all causes or non-external causes only, in periods ranging from Jan 1, 1984, to Dec 31, 2015, from various locations across the globe through the Multi-Country Multi-City Collaborative Research Network. We estimated temperature-mortality relationships through a two-stage time series design. We generated current and future daily mean temperature series under four scenarios of climate change, determined by varying trajectories of greenhouse gas emissions, using five general circulation models. We projected excess mortality for cold and heat and their net change in 1990-2099 under each scenario of climate change, assuming no adaptation or population changes. FINDINGS: Our dataset comprised 451 locations in 23 countries across nine regions of the world, including 85 879 895 deaths. Results indicate, on average, a net increase in temperature-related excess mortality under high-emission scenarios, although with important geographical differences. In temperate areas such as northern Europe, east Asia, and Australia, the less intense warming and large decrease in cold-related excess would induce a null or marginally negative net effect, with the net change in 2090-99 compared with 2010-19 ranging from -1·2% (empirical 95% CI -3·6 to 1·4) in Australia to -0·1% (-2·1 to 1·6) in east Asia under the highest emission scenario, although the decreasing trends would reverse during the course of the century. Conversely, warmer regions, such as the central and southern parts of America or Europe, and especially southeast Asia, would experience a sharp surge in heat-related impacts and extremely large net increases, with the net change at the end of the century ranging from 3·0% (-3·0 to 9·3) in Central America to 12·7% (-4·7 to 28·1) in southeast Asia under the highest emission scenario. Most of the health effects directly due to temperature increase could be avoided under scenarios involving mitigation strategies to limit emissions and further warming of the planet. INTERPRETATION: This study shows the negative health impacts of climate change that, under high-emission scenarios, would disproportionately affect warmer and poorer regions of the world. Comparison with lower emission scenarios emphasises the importance of mitigation policies for limiting global warming and reducing the associated health risks. FUNDING: UK Medical Research Council.

Center for Environmental and Respiratory Health Research University of Oulu Oulu Finland; Medical Research Center Oulu Oulu University Hospital and University of Oulu Oulu Finland

Department of Environmental Engineering Kyoto University Kyoto Japan

Department of Environmental Health Harvard TH Chan School of Public Health Boston MA USA

Department of Environmental Health National Institute of Public Health Cuernavaca Morelos Mexico

Department of Environmental Health School of Public Health Fudan University Shanghai China

Department of Environmental Health University of São Paulo São Paulo Brazil

Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Australia; Division of Epidemiology and Biostatistics School of Population Health University of Queensland Brisbane QLD Australia

Department of Epidemiology Lazio Regional Health Service Rome Italy

Department of Epidemiology Public Health and Preventive Medicine University of Ottawa Ottawa ON Canada

Department of Pediatric Infectious Diseases Institute of Tropical Medicine Nagasaki University Nagasaki Japan

Department of Public Health and Clinical Medicine Umeå University Umeå Sweden

Department of Public Health and Clinical Medicine Umeå University Umeå Sweden; Department of Clinical Science Malmö Lund University Lund Sweden

Department of Public Health National Taiwan University Taipei Taiwan

Department of Public Health Universidad de los Andes Santiago Chile

Department of Social and Environmental Health Research London School of Hygiene and Tropical Medicine London UK

Department of Social and Environmental Health Research London School of Hygiene and Tropical Medicine London UK; Environmental Change Department Centre for Radiation Chemical and Environmental Hazards Public Health England Chilton UK

Department of Social and Environmental Health Research London School of Hygiene and Tropical Medicine London UK; Institute of Occupational Medicine Edinburgh UK

Environmental and Occupational Medicine National Taiwan University and NTU Hospital Taipei Taiwan

Epidemiology and Environmental Health Joint Research Unit CIBERESP University of Valencia Valencia Spain

Faculty of Health and Sport Sciences University of Tsukuba Tsukuba Japan

Faculty of Public Health University of Medicine and Pharmacy of Ho Chi Minh City Ho Chi Minh City Vietnam

Faculty of Public Health University of Medicine and Pharmacy of Ho Chi Minh City Ho Chi Minh City Vietnam; Institute of Research and Development Duy Tan University Da Nang Vietnam

Graduate School of Public Health Seoul National University Seoul South Korea

Institute of Advanced Studies University of São Paulo São Paulo Brazil

Institute of Atmospheric Physics Academy of Sciences of the Czech Republic Prague Czech Republic

Institute of Atmospheric Physics Academy of Sciences of the Czech Republic Prague Czech Republic; Faculty of Environmental Sciences Czech University of Life Sciences Prague Czech Republic

Institute of Environment Health and Societies Brunel University London London UK

Institute of Environmental Assessment and Water Research Barcelona Spain

Potsdam Institute for Climate Impact Research Potsdam Germany

Santé Publique France French National Public Health Agency Saint Maurice France

School of Forestry and Environmental Studies Yale University New Haven CT USA

School of Physics Dublin Institute of Technology Dublin Ireland

School of Public Health and Institute of Environment and Human Health Anhui Medical University Hefei China; Shanghai Children's Medical Centre Shanghai Jiao Tong University Shanghai China; School of Public Health and Social Work Queensland University of Technology Brisbane QLD Australia

Swiss Tropical and Public Health Institute Basel Switzerland; University of Basel Basel Switzerland

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Lancet Planet Health. 2019 Mar;3(3):e121. doi: 10.1016/S2542-5196(19)30016-6. PubMed

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Lancet Planet Health. 2019 Mar;3(3):e122-e123. doi: 10.1016/S2542-5196(19)30043-9. PubMed

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