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Background: Rapid activation of the cardiac catheterization laboratory for primary percutaneous coronary intervention (PCI) improves outcomes for ST-segment elevation myocardial infarction (STEMI), but selected emphasis on minimizing time to reperfusion may lead to an increased frequency of false -positive STEMI activations (FPSA). While delays in reperfusion therapy are associated with worse outcomes, inaccurate diagnosis also has potential clinical as well as cost related repercussions. According to prior reports, FPSA rates vary between 15-52 percent.Method: We analyzed consecutive patients referred for primary PCI for a possible STEMI at a single center from November 2013 to February 2017. False-positive STEMI activation was defined as lack of electrocardiographic criteria consistent with American College of Cardiology/American Heart Association guidelines for diagnosis of STEMI, and clinical assessments. Overall differences amongst various STEMI activators were evaluated using Chi-square test. Differences between working-hours (0700-1600) versus off-hours (1601-0659) were evaluated using Cochran-Mantel-Haenszel test.Results: Of 355 STEMI activations, 194 (55%) were called by emergency physicians (ED), 81 (23%) by emergency medical services (EMS) and 80 (22%) by other (inpatient services & out of hospital transfers). A total of 120 (34%) cases occurred during working-hours and 235 (66%) cases occurred during off-hours. The average age of the study population was 62 (13) years, with 245(68%) males and average BMI of 30 (6) kg/m2. The prevalence of FPSA initiated by the ED, EMS, and others was 32 (16.5%), 9 (11%), and 14 (18%), respectively (p=0.06). Of FSPA, 40% were anterior, 25% inferior, 21% lateral, and 14% inferolateral wall infarctions. Out of 55 total FPSA, 37 (67%) occurred during the off-hours. Comparing activators based on hours, the prevalence of FPSA during off-hours initiated by the ED, EMS, and others were 69%, 66%, and 66%, respectively (p=0.6).Conclusion: In this study, approximately 1 out of 6.5 STEMI activations was a false-positive. This trend is the same during working as well as off-hours and does not differ between various STEMI activators. Improved and structured communication between cardiology, emergency medicine, and paramedic teams may promote lower false positive rates and positively impact overall delivery of care.