Background: Out-of-hospital cardiac arrest (OHCA) remains a major public health issue. Several studies have found that an increased level of ambient particulate matter (PM) smaller than 2.5 microns (PM2.5) is associated with an increased risk of OHCA. We investigated the relationship between air pollution levels and the incidence of OHCA in Perth, Western Australia. Methods: We linked St John Ambulance OHCA data of presumed cardiac aetiology with Perth air pollution data from seven monitors which recorded hourly levels of PM smaller than 2.5 and 10 microns (PM2.5/PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3). We used a case-crossover design to estimate the strength of association between ambient air pollution levels and risk of OHCA. Results: Between 2000 and 2010, there were 8551 OHCAs that met the inclusion criteria. Of these, 5624 (65.8 ) occurred in men. An IQR increase in the 24 and 48 h averages of PM2.5 was associated with 10.6 (OR 1.106, 95 CI 1.038 to 1.180) and 13.6 (OR 1.136, 95 CI 1.051 to 1.228) increases, respectively, in the risk of OHCA. CO showed a consistent association with increased risk of an OHCA. An IQR increase in the 4 h average concentration of CO was associated with a 2.2 (OR 1.022, 95 CI 1.002 to 1.042) increase in risk of an OHCA. When we restricted our analysis of CO to arrests occurring between 6:00 and 10:00, we found a 4.4 (95 CI 1.1 to 7.8 ) increase in risk of an OHCA. Conclusions: Elevated ambient PM2.5 and CO are associated with an increased risk of OHCA.