The UAS community in the United States has identified the need for a collision avoidance region in which UAS Detect-and-Avoid (DAA) vertical guidance is restricted to preclude interoperability issues with manned aircraft collision avoidance system vertical resolution advisories (RAs). This paper documents the process by which the collision avoidance region was defined. Three candidate definitions were evaluated on 1.3 million simulated pairwise encounters between UAS and manned aircraft covering a wide range of horizontal and vertical closure rates, angles, and miss distances. They were evaluated with regard to UAS DAA interoperability with manned aircraft collision avoidance systems in terms of: 1) the primary objective of restricting DAA vertical guidance before RAs when the aircraft are close, and 2) the secondary objective of avoiding unnecessary restrictions of DAA vertical guidance at a DAA alert when the aircraft are further apart. The collision avoidance region definition that fully achieves the primary objective and best achieves the secondary objective was recommended to and accepted by the UAS community in the United States. By this definition, UAS and manned aircraft are in the collision avoidance region--during which DAA vertical guidance is restricted--when the time to closest point of approach is less than 50 seconds and either the time to co-altitude is less than 50 seconds or the current vertical separation is less than 800 feet.