Study Objectives: Out-Of-Hospital Cardiac Arrest (OHCA) afflicts >350,000 people annually in the US Significant coronary artery disease is identified in the majority of OHCA cases. While coronary angiography (CAG) with percutaneous coronary intervention (PCI) as part of post-arrest management has been associated with improved survival, substantial uncertainty exists regarding patient selection for postarrest CAG. The objective of this study is to test the hypothesis that anginal symptoms immediately before OHCA are associated with significant coronary lesions identified on CAG.Methods: We performed a multicenter retrospective cohort study of adult patients who experienced atraumatic out-of-hospital cardiac arrest (OHCA) with successful initial resuscitation and subsequent CAG, who presented to the emergency department of eight hospitals in Southeastern Pennsylvania and Delaware between 1/2015-12/2019. We used electronic medical records and EMS patient care reports to record out-of-hospital report of anginal symptoms (eg, chest discomfort, shortness of breath) prior to OHCA onset, as well as clinical factors available to providers during post-arrest care, such as prior history of myocardial infarction, initial arrest rhythm, and sex. The primary outcome was the presence of significant coronary lesions (defined as >50% stenosis of the left main or >75% stenosis of other coronary arteries) on post-arrest CAG; secondary outcomes included performance of PCI and survival to discharge. Multivariable logistic regression was performed, adjusting for demographic variables, pre-arrest chest discomfort, and other factors.Results: 400 resuscitated OHCA patients with subsequent CAG were included. Median age was 59 y (IQR 51-69 y), and 31% were female, and 24% of patients reported pre-arrest chest discomfort. At least one significant stenosis was found in 62% of cases, of which 71% received PCI. Clinical factors independently associated with a significant lesion included a history of myocardial infarction (aOR 6.5 [95% CI 1.3-32.4], p¼0.02), pre-arrest chest discomfort (aOR 4.8 [95% CI 2.1 -11.8], p¼<0.001), ST-segment elevations (aOR 3.2 [95% CI 1.7-6.3], p<0.001), male sex (aOR 2.0 [95% CI 1.0-3.7], p¼0.04) and an initial shockable rhythm (aOR 1.9 [95% CI 1.0-3.4], p¼0.05).Conclusions: History of pre-arrest chest discomfort, prior myocardial infarction, and initial shockable rhythms were significantly and independently associated with significant coronary artery lesions. Surprisingly, the presence of chest discomfort was more strongly associated with significant disease than the presence of ST-segment elevations.