One of the most critical challenges to full integration of unmanned aircraft systems (UAS) into the National Airspace System (NAS) is the requirement to comply with CFR 14 Part 91.113 to “see and avoid” other aircraft. Various attempts have been made to develop systems to “sense and avoid” other aircraft so UAS can comply with the intent of the regulation. This article proposes a framework to develop effectiveness requirements for any SAA system by linking UAS characteristics and operating environments to midair collision risk quantified by a fatality rate. The framework consists of a target level of safety (TLS) approach using an event tree format. Safety has been identified as the most important consideration in the UAS integration process. While safety can be defined in many ways, the authors propose using a fatality rate metric that follows other statistics used in the industry. This metric allows for the use of a TLS approach to the development of SAA requirements for system certification. Failure to adequately link system requirements to safety could result in the implementation of SAA systems that either do not adequately mitigate the risk associated with UAS operations or are overdesigned, resulting in increased cost and complexity. This article demonstrates the use of the proposed framework to develop specific SAA effectiveness standards based on UAS weight and airspace class combinations.