The rapid spread of Zika virus across the World Health Organization's Region of the Americas has had a direct effect on the U.S. health care delivery system. Hospitals in New York City (NYC) have been implementing prevention and response efforts consistent with CDC guidance. As of September 21, 2016, a total of 715 cases of laboratory-confirmed Zika virus disease had been diagnosed in New York state among travelers who returned from affected areas, their sexual contacts, or infants infected in utero. This represents the highest number of reported cases in any state to date, and underscores the importance of health care systems preparing to care for patients with possible Zika virus disease (1). Building upon a framework that was established in 2014 to screen patients for possible exposure to Ebola virus disease (Ebola), NYC Health + Hospitals,* the largest municipal health care delivery system in the United States, implemented a Zika Preparedness and Response Action Plan† (Zika Action Plan) to address the threat from Zika and ensure appropriate patient care. The plan developed by NYC Health + Hospitals includes universal travel screening, signage depicting areas with active Zika virus transmission, clinical and epidemiologic evaluation for possible Zika virus exposure, diagnostic testing for Zika virus infection and linking of infected patients to appropriate specialists, and education on Zika virus disease and preventive measures (e.g., avoiding travel to areas with active Zika virus transmission).