Introduction <p>Methotrexate is a cornerstone disease-modifying antirheumatic drug for rheumatoid arthritis (RA), effectively controlling disease activity and reducing cardiovascular mortality. Despite its efficacy, parenteral methotrexate, which offers higher bioavailability, faster response, and fewer gastrointestinal side effects compared to oral administration, remains underutilized in clinical practice. Understanding the factors influencing its utilization is critical to improving RA management.</p> Aim <p>To explore the barriers and enablers towards using parenteral methotrexate in rheumatoid arthritis patients from the perspective of Australian healthcare professionals (HCPs).</p> Method <p>A qualitative study was conducted using semi-structured interviews between May and August 2022. Participants were recruited via advertising and snowballing. The Theoretical Domains Framework was used to guide the development of the interview guide and data analysis (directed content analysis), supplemented by conventional content analysis (inductive content analysis) to identify emergent themes.</p> Results <p>Nineteen HCPs (57.9% male, 42.1% female, 63.2% with more than 10&#xa0;years of experience) were interviewed, including 14 rheumatologists, 3 pharmacists and 2 nurses. Findings related to domains “environmental context and resources”, “social influences” and “skills” were frequently identified, whereas the domains “intention”, “reinforcement” and “emotion” were least reported. The most prominent enablers related to HCPs' knowledge and skills. Necessary skills were grouped into communication, logistical planning, and patient selection. Other enablers included the accessibility of injection support services, availability of prefilled syringes and online resources for patients (“environmental context and resources”) and social influences. The most common identified barriers related to the logistics of implementing parenteral methotrexate. Other barriers included issues with the Occupational Health and Safety guidelines, time constraints (“environmental context and resources”), concerns about patients withdrawing methotrexate from the vial (“emotion”) and patients’ low acceptability or affordability of the injectable medication (“social influences”).</p> Conclusion <p>Our findings suggest that training and guidance on selecting appropriate patients, utilization of systems to support education of patients and to minimize occupational exposure, and availability of patient-friendly devices would support greater implementation of parenteral methotrexate in practice.</p>