Introduction: Few studies have investigated the management of COVID-19 cases from the operational perspective of the emergency department (ED). We sought to compare the management and outcome of COVID-19 positive and negative patients who presented to French EDs. Methods: We conducted a prospective, multicenter, observational study in four EDs. Included in the study were adult patients (≥18 years) between March 6–May 10, 2020, were hospitalized, and whose presenting symptoms were evocative of COVID-19. We compared the clinical features, management, and prognosis of patients according to their confirmed COVID-19 status. Results: Of the 2,686 patients included in this study, 760 (28.3%) were COVID-19 positive. Among them, 364 (48.0%) had hypertension, 228 (30.0%) had chronic cardiac disease, 186 (24.5%) had diabetes, 126 (16.6%) were obese, and 114 (15.0%) had chronic respiratory disease. The proportion of patients admitted to intensive care units (ICU) was higher among COVID-19 positive patients (185/760, 24.3%) compared to COVID-19 negative patients (206/1,926, 10.7%; P <0.001), and they required mechanical ventilation (89, 11.9% vs 37, 1.9%; P <0.001) and high-flow nasal cannula oxygen therapy (135, 18.1% vs 41, 2.2%; P < 0.001) more frequently. The in-hospital mortality was significantly higher among COVID-19 positive patients (139, 18.3% vs 149, 7.7%; P <0.001). Conclusion: Emergency departments were on the frontline during the COVID-19 pandemic and had to manage potential COVID-19 patients. Understanding what happened in the ED during this first outbreak is crucial to underline the importance of flexible organizations that can quickly adapt the bed capacities to the incoming flow of COVID-19 positive patients.