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Background: While the indication for noninvasive ventilation (NIV) in severely hypoxemic patients with acute heart failure (AHF) is often indicated and may improve clinical course, the benefit of early initiation before patient arrival to the emergency department (ED) remains unknown., Objective: This study aimed to assess the impact of early initiation of NIV during emergency medical service (EMS) transportation on outcomes in patients with AHF., Design: A secondary retrospective analysis of the EAHFE (Epidemiology of AHF in EDs) registry., Setting: Fifty-three Spanish EDs., Participants: Patients with AHF transported by EMS physician-staffed ambulances who were treated with NIV at any time during of their emergency care were included and categorized into two groups based on the place of NIV initiation: prehospital (EMS group) or ED (ED group)., Outcome Measures: Primary outcome was the composite of in-hospital mortality and 30-day postdischarge death, readmission to hospital or return visit to the ED due to AHF. Secondary outcomes included 30-day all-cause mortality after the index event (ED admission) and the different component of the composite primary endpoint considered individually. Multivariate logistic regressions were employed for analysis., Results: Out of 2406 patients transported by EMS, 487 received NIV (EMS group: 31%; EMS group: 69%). Mean age was 79 years, 48% were women. The EMS group, characterized by younger age, more coronary artery disease, and less atrial fibrillation, received more prehospital treatments. The adjusted odds ratio (aOR) for composite endpoint was 0.66 (95% CI: 0.42-1.05). The aOR for secondary endpoints were 0.74 (95% CI: 0.38-1.45) for in-hospital mortality, 0.74 (95% CI: 0.40-1.37) for 30-day mortality, 0.70 (95% CI: 0.41-1.21) for 30-day postdischarge ED reconsultation, 0.80 (95% CI: 0.44-1.44) for 30-day postdischarge rehospitalization, and 0.72 (95% CI: 0.25-2.04) for 30-day postdischarge death., Conclusion: In this ancillary analysis, prehospital initiation of NIV in patients with AHF was not associated with a significant reduction in short-term outcomes. The large confidence intervals, however, may preclude significant conclusion, and all point estimates consistently pointed toward a potential benefit from early NIV initiation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)