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BACKGROUND AND IMPORTANCE Chest pain is one of the most common presentations to the emergency department (ED). The HEART-score is used to assess the 30-day risk of developing a major adverse cardiac event (MACE). The HEART-score enables clinicians to classify patients in low, intermediate, or high-risk groups though little is known as to whether this can be done reliably and reproducibly in a prehospital setting. OBJECTIVE The aim of this study was to compare the interobserver agreement of the HEART-score between ambulance nurses and ED physicians. DESIGN, SETTINGS, AND PARTICIPANTS Patients ≥18 years, with chest pain of suspected cardiac origin presented by ambulance to the EDs of four regional hospitals, were prospectively enrolled between October 2018 and April 2019. OUTCOMES MEASURE AND ANALYSIS The primary endpoint was interobserver agreement of the HEART-scores calculated by ambulance nurses compared to those calculated by ED physicians. Agreement was measured using Cohen's Kappa (K) both for overall HEART-score and dichotomized HEART categories. A secondary endpoint was the occurrence of a MACE at 30 days after inclusion. MAIN RESULTS A total of 307 patients were enrolled of which 166 patients were male (54%). The mean age was 64.8 years. In 23% (95% confidence interval, 18-27), patients were scored in the low-risk category by both ambulance nurses and ED physicians. The K for the overall HEART-score compared between ambulance nurses and ED physicians was 0.514. The K for the low-risk category versus intermediate and high-risk category was 0.591. Both are defined as 'moderate'. MACE within 30 days occurred in 64 patients (21%). In the low-risk group as defined by the ambulance nurses, there was a 7% risk of MACE compared to an average 5% MACE risk in the ED physician group. CONCLUSIONS The moderate interobserver agreement of the HEART-score does not currently support the use of the HEART-score by ambulance nurses in a prehospital setting. Training for prehospital nurses is vital to ensure that they are able to calculate the HEART-score accurately.