Background <p>Automatic substitution of biological medicines refers to a dispensing practice in community pharmacies in which a pharmacist substitutes a prescribed biological medicine with an interchangeable biologic product without contacting the prescriber. Automatic substitution of biological medicines in community pharmacies offers one possibility to reduce increased healthcare expenditures through price competition among biological medicines. The implementation of automatic substitution requires active engagement, information and coordination to maintain medication safety. Research on healthcare professionals’ perceptions towards automatic substitution remains limited. This study provides insight into automatic substitution from the perspective of rheumatology nurses, whose role in rheumatology patient care is essential. The Aim of the study was to explore rheumatology nurses’ perceptions of automatic substitution of biological medicines and its safe implementation.</p> Methods <p>Data were collected through individual semi-structured interviews in 2025. The participants were rheumatology nurses (<i>n</i> = 10) with clinical experience in patient care, including injection and device guidance for patients. The data were analysed with inductive content analysis. To ensure comprehensive and transparent reporting, the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist was utilised.</p> Results <p>Four categories were identified: (1) Perceptions of automatic substitution, (2) Factors supporting the implementation of automatic substitution, (3) Concerns related to automatic substitution, and (4) Safe implementation of automatic substitution. All interviewees acknowledged the critical roles of community pharmacies and healthcare personnel in ensuring safe implementation. Perceptions of automatic substitution were positive, although concerns were raised about medication-related issues and work-related challenges such as increased workload in patient counselling. Factors supporting the implementation of automatic substitution were mainly related to the suitability of biological medicines for substitution, and patients’ experience of biological medicines and generic substitution.</p> Conclusions <p>Rheumatology nurses’ perceptions of automatic substitution were generally positive, and they considered biological medicines suitable for substitution. However, their concerns regarding work-related challenges and medication-related issues highlight the importance of ensuring sufficient resources to sustain patient safety. Successful and safe implementation of automatic substitution will require comprehensive patient counselling.</p>