The self-separation concept of operations aims to provide an efficient solution to the management of the expected radical increase of air traffic. The major features of this air traffic management (ATM) concept concern the delegation of the separation task from the air traffic controllers to the flight crew for a defined part of the airspace. A major prerequisite of the full-scale implementation of the self-separation concept is the examination of its institutional and economic feasibility. This study provides the methodological steps for identification of possible legal and institutional barriers and enablers to the introduction of such a concept as well as an analysis of the concept's economic viability. The expected outcome of the institutional analysis is the determination of the changes in the existing institutional framework that may facilitate introduction of the new concept. Cost-benefit analysis (CBA) is applied for the economic appraisal of ATM changes proposed in the concept. Given that the self-separation concept of operations is in its definition phase, scarcity of cost and benefit data is encountered. A methodological framework is proposed for applying the CBA for this type of ATM operational concept. Applying the institutional analysis for Europe indicated that changes in the relevant regulatory framework should be in place to deploy the proposed concept. Moreover, exemplary results from the application of the proposed CBA framework in Europe encourage the development of the self-separation concept of operations to the next maturity stage.