Background: Biologics are used as effective therapeutics to treat a variety of diseases. Even though biologics are widely used, knowledge on the post-marketing experience of patients is limited. Therefore, a framework was established for a patient-reported outcome measure (PROM)-based drug safety monitoring system for ADRs attributed to biologics, known as the ‘Dutch Biologic Monitor’. Objective: Generation of a multi-stakeholder perspective on the preferred setup, potential and added value of a PROM-based national drug safety monitoring system. Methods: Nineteen stakeholders were interviewed following a structured interview guide. Transcribed data were coded and analyzed to count frequencies and to generate recurring themes. Results: Stakeholders (84.2%) support the establishment of a national drug safety monitoring system, but the feasibility depends on the implementation process. The need for integration and assessment of PROMs on ADRs in clinical practice and the preference to monitor small molecules and new drugs were emphasized. Preferably, all pharmacological options per indication should be monitored. Conclusions: Stakeholders recommend to establish a PROM-based national drug safety monitoring system focused on ADRs attributed to biologics, small molecules, and new drugs. Moreover, PROMs on ADRs ideally need to become integrated in clinical practice to provide health-care providers more insight in patients’ perspectives.