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Background: Apart from cost-effectiveness, considerations like equity and acceptability may affect health-care priority setting. Preferably, priority setting combines evidence evaluation with an appraisal procedure, to elicit and weigh these considerations., Objective: To demonstrate a structured approach for eliciting and evaluating a broad range of assessment criteria, including key stakeholders' values, aiming to support decision makers in priority setting., Methods: For a set of cost-effective substitute interventions for depression care, the appraisal criteria were adopted from the Australian Assessing Cost-Effectiveness initiative. All substitute interventions were assessed in an appraisal, using focus group discussions and semi-structured interviews conducted among key stakeholders., Results: Appraisal of the substitute cost-effective interventions yielded an overview of considerations and an overall recommendation for decision makers. Two out of the thirteen pairs were deemed acceptable and realistic, that is investment in therapist-guided and Internet-based cognitive behavioural therapy instead of cognitive behavioural therapy in mild depression, and investment in combination therapy rather than individual psychotherapy in severe depression. In the remaining substitution pairs, substantive issues affected acceptability. The key issues identified were as follows: workforce capacity, lack of stakeholder support and the need for change in clinicians' attitude., Conclusions: Systematic identification of stakeholders' considerations allows decision makers to prioritize among cost-effective policy options. Moreover, this approach entails an explicit and transparent priority-setting procedure and provides insights into the intended and unintended consequences of using a certain health technology., Patient Contribution: Patients were involved in the conduct of the study for instance, by sharing their values regarding considerations relevant for priority setting., (© 2021 The Authors. Health Expectations published by John Wiley & Sons Ltd.)