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Background: Acute Coronary Syndrome (ACS), with or without ST-segment elevation, is a major contributor to global mortality and morbidity. Swift diagnosis and treatment are vital for mitigating cardiac damage and improving long-term outcomes. The 12-lead electrocardiogram (ECG) currently serves as the gold standard for diagnosis in ACS with ST-segment elevation and may support the diagnosis in ACS without ST-segment elevation. However, the growing prevalence of smartwatches enables the acquisition of electrocardiographic data without traditional ECG equipment. While smaller studies support smartwatch ECG use, larger-scale validation within ACS remains lacking. The ACS WATCH II study aims to validate smartwatch ECG recordings for ACS. Methods: The primary objective is to validate smartwatch-obtained electrocardiographic data in patients presenting with ACS. Two cohorts of 120 patients each, presenting ACS with and without ST-segment elevation, will be assessed. Smartwatches will capture recordings of leads I, III, and V2 alongside standard ECGs. These leads, chosen due to a 97% ACS diagnosis sensitivity in previous studies, will undergo blind evaluation by two experienced external assessors against conventional ECG. Additionally, a control sample of 60 healthy individuals will be included. Conclusions: ACS WATCH II pioneers large-scale prospective validation of smartwatch ECG recordings in ACS patients. Additionally, it indirectly validates a swift diagnostic approach using three leads (I, III, and V2). This could expedite time-critical ACS diagnoses and simplify access through smartwatch-based diagnosis. [ABSTRACT FROM AUTHOR]