The rapid spread of Zika virus represents a threat to public health and demands significant preparation from hospitals and health care systems. Establishment of procedures for the identification of cases of Zika virus infection is a fundamental aspect of response planning. We describe the steps taken in the development and implementation of a protocol for the diagnosis and management of suspected cases of Zika virus infection in a large academic medical center. (Disaster Med Public Health Preparedness. 2017;11:256–258)