Out-of-hospital cardiac arrests (OHCAs) are a major public health concern and a leading cause of death worldwide. Exposure to ambient air pollution is associated with increases in morbidity and mortality and has been recognized as a leading contributor to global disease burden. To examine the association between short-term exposure to particulate matter with a diameter of 2.5 μm or smaller (PM2.5) and the incidence of OHCAs of cardiac origin and with the development of initial cardiac arrest rhythm. This case-control study used data from cases registered between January 1, 2005, and December 31, 2016, in the All-Japan Utstein Registry, a prospective, nationwide, population-based database for OHCAs across all 47 Japanese prefectures. These OHCA cases included patients who had bystander-witnessed OHCAs and for whom emergency medical services responders initiated resuscitation before hospital transfer. A case-crossover design was employed for the study analyses. A prefecture-specific, conditional logistic regression model to estimate odds ratios was applied, and a random-effects meta-analysis was used to obtain prefecture-specific pooled estimates. All analyses were performed from May 7, 2019, to January 23, 2020. The main outcome was the association of short-term PM2.5 exposure with the incidence of bystander-witnessed OHCAs of cardiac origin. The differences in the distribution of initial cardiac arrest rhythm in OHCAs among those with exposure to PM2.5 were also examined. In total, 103 189 OHCAs witnessed by bystanders were included in the final analysis. Among the patients who experienced such OHCAs, the mean (SD) age was 75 (15.5) years, and 62 795 (60.9%) were men. Point estimates of the percentage increase for a 10-μg/m3 increase in PM2.5 at lag0-1 (difference in mean PM2.5 concentrations measured on the case day and 1 day before) demonstrated a statistically significantly higher incidence of OHCA across most of the 47 prefectures, without significant heterogeneity (I2 = 20.1%; P = .12). A stratified analysis found an association between PM2.5 exposure and OHCAs (% increase, 1.6; 95% CI, 0.1%-3.1%). An initial shockable rhythm, such as ventricular fibrillation or pulseless ventricular tachycardia (% increase, 0.6; 95% CI, -2.0% to 3.2%), was not associated with PM2.5 exposure. However, an initial nonshockable rhythm, such as pulseless electrical activity and asystole, was associated with PM2.5 exposure (% increase, 1.4; 95% CI, 0.1%-2.7%). Findings from this study suggest that increased PM2.5 concentration is associated with bystander-witnessed OHCA of cardiac origin that commonly presents with nonshockable rhythm. The results support measures to reduce PM2.5 exposure to prevent OHCAs of cardiac origin.