Background Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM 2•5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM 2•5 and mortality across various regions of the world.Methods For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfirerelated PM 2•5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0•25° × 0•25° resolution. The association between wildfire-related PM 2•5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM 2•5 exposure was calculated.Findings 65•6 million all-cause deaths, 15•1 million cardiovascular deaths, and 6•8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 µg/m³ increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM 2•5 exposure were 1•019 (95% CI 1•016-1•022) for all-cause mortality, 1•017 (1•012-1•021) for cardiovascular mortality, and 1•019 (1•013-1•025) for respiratory mortality. Overall, 0•62% (95% CI 0•48-0•75) of all-cause deaths, 0•55% (0•43-0•67) of cardiovascular deaths, and 0•64% (0•50-0•78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM 2•5 exposure during the study period.Interpretation Short-term exposure to wildfire-related PM 2•5 was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires.