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OBJECTIVE To quantify the dose-response relationship between moderate to vigorous physical activity and primary cardiac arrest (PCA). PATIENTS AND METHODS There were 504,840 participants older than 18 years who underwent the Korean National Health Screening Program, including a self-administered questionnaire for physical activity from January 1, 2009, through December 31, 2014. Physical activity levels were converted into metabolic equivalent tasks (METs) per week and categorized to correspond with multiples of public health recommendations. We evaluated the quantitative and categorical dose-response relationship between physical activity and PCA. RESULTS A curvilinear dose-response relationship between physical activity and PCA was observed; the benefits started at two-thirds (5 MET-hour/week) of the United States and World Health Organization guidelines-recommended minimum (7.5 MET-hour/week) and continued to 5 times (40 MET-hour/week) the recommended minimum (P nonlinearity <.001). The largest benefit was noted at a level of 2 to 3 times the recommended minimum (hazard ratio, 0.6; 95% CI, 0.4 to 0.8). In addition, there was no evidence of an increased PCA risk at a level more than 5 times the recommended minimum (hazard ratio, 0.7; 95% CI, 0.5 to 1.1). These associations were consistent regardless of age, sex, body mass index, comorbid conditions, and estimated 10-year risk for cardiovascular disease. CONCLUSION The beneficial effect of physical activity on PCA started at two-thirds of the recommended minimum and continued to 5 times the recommended minimum. No excess risk for PCA was present among individuals with activity levels more than 5 times the recommended minimum regardless of cardiovascular disease or lifestyle risk factor presence.