© 2015, Public Health Services, US Dept of Health and Human Services. All rights reserved. Background: Millions of people can potentially be exposed to smoke from forest fires, making this an important public health problem in many countries. Objective: In this study we aimed to measure the association between out-of-hospital cardiac arrest (OHCA) and forest fire smoke exposures in a large city during a severe forest fire season, and estimate the number of excess OHCAs due to the fire smoke. Methods: We investigated the association between particulate matter (PM) and other air pollutants and OHCA using a case-crossover study of adults (≥ 35 years of age) in Melbourne, Australia. Conditional logistic regression models were used to derive estimates of the percent change in the rate of OHCA associated with an interquartile range (IQR) increase in exposure. From July 2006 through June 2007, OHCA data were collected from the Victorian Ambulance Cardiac Arrest Registry. Hourly air pollution concentrations and meteorological data were obtained from a central monitoring site. Results: There were 2,046 OHCAs with presumed cardiac etiology during our study period. Among men during the fire season, greater increases in OHCA were observed with IQR increases in the 48-hr lagged PM with diameter ≤ 2.5 μm (PM2.5) (8.05%; 95% CI: 2.30, 14.13%; IQR = 6.1 μg/m3) or ≤ 10 μm (PM10) (11.1%; 95% CI: 1.55, 21.48%; IQR = 13.7 μg/m3) and carbon monoxide (35.7%; 95% CI: 8.98, 68.92%; IQR = 0.3 ppm). There was no significant association between the rate of OHCA and air pollutants among women. One hundred seventyfour “fire-hours” (i.e., hours in which Melbourne’s air quality was affected by forest fire smoke) were identified during 12 days of the 2006/2007 fire season, and 23.9 (95% CI: 3.1, 40.2) excess OHCAs were estimated to occur due to elevations inPM2.5 during these fire-hours. Conclusions: This study found an association between exposure to forest fire smoke and an increase in the rate of OHCA. These findings have implications for public health messages to raise community awareness and for planning of emergency services during forest fire seasons.