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Background Studies have reported significant reduction in acute myocardial infarction-related hospitalizations during the coronavirus disease 2019 (COVID-19) pandemic. However, whether these trends are associated with increased incidence of out-of-hospital cardiac arrest (OHCA) in this population is unknown. Methods and Results Acute myocardial infarction hospitalizations with OHCA during the COVID-19 period (February 1-May 14, 2020) from the Myocardial Ischaemia National Audit Project and British Cardiovascular Intervention Society data sets were analyzed. Temporal trends were assessed using Poisson models with equivalent pre-COVID-19 period (February 1-May 14, 2019) as reference. Acute myocardial infarction hospitalizations during COVID-19 period were reduced by >50% (n=20 310 versus n=9325). OHCA was more prevalent during the COVID-19 period compared with the pre-COVID-19 period (5.6% versus 3.6%), with a 56% increase in the incidence of OHCA (incidence rate ratio, 1.56; 95% CI, 1.39-1.74). Patients experiencing OHCA during COVID-19 period were likely to be older, likely to be women, likely to be of Asian ethnicity, and more likely to present with ST-segment-elevation myocardial infarction. The overall rates of invasive coronary angiography (58.4% versus 71.6%; P <0.001) were significantly lower among the OHCA group during COVID-19 period with increased time to reperfusion (mean, 2.1 versus 1.1 hours; P =0.05) in those with ST-segment-elevation myocardial infarction. The adjusted in-hospital mortality probability increased from 27.7% in February 2020 to 35.8% in May 2020 in the COVID-19 group ( P <.001). Conclusions In this national cohort of hospitalized patients with acute myocardial infarction, we observed a significant increase in incidence of OHCA during COVID-19 period paralleled with reduced access to guideline-recommended care and increased in-hospital mortality.