Abstract Aims Globally, nearly 20% of cardiovascular disease deaths were attributable to air pollution. Out-of-hospital cardiac arrest (OHCA) represents a major public health problem; therefore, the identification of novel OHCA triggers is of crucial relevance. The aim of the study was to evaluate the association between air pollution (short-, mid-, and long-term exposures) and OHCA risk, during a 7-year period in a highly polluted urban area in northern Italy, with a high density of automated external defibrillators (AEDs). Methods and results Out-of-hospital cardiac arrests were prospectively collected from the ‘Progetto Vita Database’ between 1 January 2010 and 31 December 2017; day-by-day air pollution levels were extracted from the Environmental Protection Agency stations. Electrocardiograms of OHCA interventions were collected from the AED data cards. Day-by-day particulate matter (PM) 2.5 and 10, ozone (O3), carbon monoxide (CO), and nitrogen dioxide (NO2) levels were measured. A total of 880 OHCAs occurred in 748 days. A significant increase in OHCA risk with a progressive increase in PM2.5, PM10, CO, and NO2 levels was found. After adjustment for temperature and seasons, a 9% and 12% increase in OHCA risk for each 10 μg/m3 increase in PM10 (P < 0.0001) and PM2.5 (P < 0.0001) levels was found. Air pollutant levels were associated with both asystole and shockable rhythm risk, while no correlation was found with pulseless electrical activity. Conclusion Short- and mid-term exposures to PM2.5 and PM10 are independently associated with the risk of OHCA due to asystole or shockable rhythm.