Background: During the COVID-19 pandemic, Central COVID-19 Coordination Centers (CCCCs) have been established at several hospitals across Germany with the intention to assist local health care professionals in efficiently referring patients with suspected or confirmed SARS-CoV-2 infection to regional hospitals and therefore to prevent the collapse of local health system structures. In addition, these centers coordinate interhospital transfers of patients with COVID-19 and provide or arrange specialized telemedical consultations., Objective: This study describes the establishment and management of a CCCC at a German university hospital., Methods: We performed economic analyses (cost, cost-effectiveness, use, and utility) according to the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) criteria. Additionally, we conducted a systematic review to identify publications on similar institutions worldwide. The 2 months with the highest local incidence of COVID-19 cases (December 2020 and January 2021) were considered., Results: During this time, 17.3 requests per day were made to the CCCC regarding admission or transfer of patients with COVID-19. The majority of requests were made by emergency medical services (601/1068, 56.3%), patients with an average age of 71.8 (SD 17.2) years were involved, and for 737 of 1068 cases (69%), SARS-CoV-2 had already been detected by a positive polymerase chain reaction test. In 59.8% (639/1068) of the concerned patients, further treatment by a general practitioner or outpatient presentation in a hospital could be initiated after appropriate advice, 27.2% (291/1068) of patients were admitted to normal wards, and 12.9% (138/1068) were directly transmitted to an intensive care unit. The operating costs of the CCCC amounted to more than €52,000 (US $60,031) per month. Of the 334 patients with detected SARS-CoV-2 who were referred via EMS or outpatient physicians, 302 (90.4%) were triaged and announced in advance by the CCCC. No other published economic analysis of COVID-19 coordination or management institutions at hospitals could be found., Conclusions: Despite the high cost of the CCCC, we were able to show that it is a beneficial concept to both the providing hospital and the public health system. However, the most important benefits of the CCCC are that it prevents hospitals from being overrun by patients and that it avoids situations in which physicians must weigh one patient's life against another's., (©Nikolas Schopow, Georg Osterhoff, Nikolaus von Dercks, Felix Girrbach, Christoph Josten, Sebastian Stehr, Pierre Hepp. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 18.11.2021.)