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Background Extreme heat has significant impacts on mortality. In Canada, past research has analyzed the degree to which non-accidental mortality increases during single extreme heat events; however, few studies have considered multiple causes of death and the impacts of extreme heat events on mortality over longer time periods. Data and methods Daily death counts attributable to non-accidental, cardiovascular, and respiratory causes were retrieved for the 12 most populous cities in Canada from 2000 to 2020. Generalized additive models were applied to quantify daily mortality risks for people aged younger than 65 years and for those aged 65 years and older in each city and for each cause of death. Model results were used to calculate the change in mortality risks and the number of excess deaths attributable to extreme heat during extreme heat events. Results Elevated mortality risks were observed during extreme heat events in most cities for non-accidental and respiratory causes. The impacts of extreme heat on non-accidental mortality were typically greater for people aged 65 and older than for those aged younger than 65. Significantly higher non-accidental mortality risks were observed during extreme heat events for people aged 65 and older in Montréal, the city of Québec, Surrey, and Toronto. For cardiovascular and respiratory causes, people aged 65 and older had significantly higher mortality risks during extreme heat events in Montréal, and both Montréal and Toronto, respectively. In the 12 cities, approximately 670 excess non-accidental deaths, 115 excess cardiovascular deaths, and 115 excess respiratory deaths were attributable to extreme heat events during the study period. Mortality risks during extreme heat events were generally higher in cities with larger proportions of renter households and fewer extreme heat events. Interpretation This study estimates the longer-term impacts of extreme heat events on three mortality outcomes in a set of large Canadian cities. As climate change causes more frequent and intense extreme heat events, and as policy makers aim to reduce the health impacts of heat, it is important to understand how and where extreme heat affects health. [ABSTRACT FROM AUTHOR]